Flexible actuator mandrel for tissue apposition systems

ABSTRACT

The invention provides devices, systems and methods for tissue approximation and repair at treatment sites. The devices, systems and methods of the invention will find use in a variety of therapeutic procedures, including endovascular, minimally-invasive, and open surgical procedures, and can be used in various anatomical regions, including the abdomen, thorax, cardiovascular system, heart, intestinal tract, stomach, urinary tract, bladder, lung, and other organs, vessels, and tissues. The invention is particularly useful in those procedures requiring minimally-invasive or endovascular access to remote tissue locations, where the instruments utilized must negotiate long, narrow, and tortuous pathways to the treatment site. In addition, many of the devices and systems of the invention are adapted to be reversible and removable from the patient at any point without interference with or trauma to internal tissues.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates generally to medical methods, devices, andsystems. In particular, the present invention relates to methods,devices, and systems for the endovascular, percutaneous or minimallyinvasive surgical treatment of bodily tissues, such as tissueapproximation or valve repair. More particularly, the present inventionrelates to repair of valves of the heart and venous valves.

Surgical repair of bodily tissues often involves tissue approximationand fastening of such tissues in the approximated arrangement. Whenrepairing valves, tissue approximation includes coapting the leaflets ofthe valves in a therapeutic arrangement which may then be maintained byfastening or fixing the leaflets. Such coaptation can be used to treatregurgitation which most commonly occurs in the mitral valve.

Mitral valve regurgitation is characterized by retrograde flow from theleft ventricle of a heart through an incompetent mitral valve into theleft atrium. During a normal cycle of heart contraction (systole), themitral valve acts as a check valve to prevent flow of oxygenated bloodback into the left atrium. In this way, the oxygenated blood is pumpedinto the aorta through the aortic valve. Regurgitation of the valve cansignificantly decrease the pumping efficiency of the heart, placing thepatient at risk of severe, progressive heart failure.

Mitral valve regurgitation can result from a number of differentmechanical defects in the mitral valve or the left ventricular wall. Thevalve leaflets, the valve chordae which connect the leaflets to thepapillary muscles, the papillary muscles or the left ventricular wallmay be damaged or otherwise dysfunctional. Commonly, the valve annulusmay be damaged, dilated, or weakened limiting the ability of the mitralvalve to close adequately against the high pressures of the leftventricle.

The most common treatments for mitral valve regurgitation rely on valvereplacement or repair including leaflet and annulus remodeling, thelatter generally referred to as valve annuloplasty. A recent techniquefor mitral valve repair which relies on suturing adjacent segments ofthe opposed valve leaflets together is referred to as the “bow-tie” or“edge-to-edge” technique. While all these techniques can be veryeffective, they usually rely on open heart surgery where the patient'schest is opened, typically via a sternotomy, and the patient placed oncardiopulmonary bypass. The need to both open the chest and place thepatient on bypass is traumatic and has associated high mortality andmorbidity. More recently, minimally invasive catheter based procedureshave been developed to deliver implantable clips to the incompetentvalve. These clips are used to fasten a portion of the valve leafletstogether, thereby reducing the regurgitation. While the clips appear tobe promising, in certain situations, delivery and deployment of the clipcan be challenging.

For these reasons, it would be desirable to provide improved methods,devices, and systems for performing the repair of mitral and othercardiac valves. Such methods, devices, and systems should preferably notrequire open chest access and be capable of being performed eitherendovascularly, i.e., using devices which are advanced to the heart froma point in the patient's vasculature remote from the heart or by aminimally invasive approach. Further, such devices and systems shouldprovide features which allow easier delivery of fixation devices, aswell as repositioning and optional removal of the fixation device priorto fixation to ensure optimal placement. Still more preferably, themethods, devices, and systems would be useful for repair of tissues inthe body other than heart valves. At least some of these objectives willbe met by the inventions described hereinbelow.

2. Description of the Background Art

Minimally invasive and percutaneous techniques for coapting andmodifying mitral valve leaflets to treat mitral valve regurgitation aredescribed in PCT Publication Nos. WO 98/35638; WO 99/00059; WO 99/01377;and WO 00/03759.

Maisano et al. (1998) Eur. J. Cardiothorac. Surg. 13:240-246; Fucci etal. (1995) Eur. J. Cardiothorac. Surg. 9:621-627; and Umana et al.(1998) Ann. Thorac. Surg. 66:1640-1646, describe open surgicalprocedures for performing “edge-to-edge” or “bow-tie” mitral valverepair where edges of the opposed valve leaflets are sutured together tolessen regurgitation. Dec and Fuster (1994) N. Engl. J. Med.331:1564-1575 and Alvarez et al. (1996) J. Thorac. Cardiovasc. Surg.112:238-247 are review articles discussing the nature of and treatmentsfor dilated cardiomyopathy.

Mitral valve annuloplasty is described in the following publications.Bach and Bolling (1996) Am. J. Cardiol. 78:966-969; Kameda et al. (1996)Ann. Thorac. Surg. 61:1829-1832; Bach and Bolling (1995) Am. Heart J.129:1165-1170; and Bolling et al. (1995) 109:676-683. Linear segmentalannuloplasty for mitral valve repair is described in Ricchi et al.(1997) Ann. Thorac. Surg. 63:1805-1806. Tricuspid valve annuloplasty isdescribed in McCarthy and Cosgrove (1997) Ann. Thorac. Surg. 64:267-268;Tager et al. (1998) Am. J. Cardiol. 81:1013-1016; and Abe et al. (1989)Ann. Thorac. Surg. 48:670-676.

Percutaneous transluminal cardiac repair procedures are described inPark et al. (1978) Circulation 58:600-608; Uchida et al. (1991) Am.Heart J. 121: 1221-1224; and Ali Khan et al. (1991) Cathet. Cardiovasc.Diagn. 23:257-262.

Endovascular cardiac valve replacement is described in U.S. Pat. Nos.5,840,081; 5,411,552; 5,554,185; 5,332,402; 4,994,077; and 4,056,854.See also U.S. Pat. No. 3,671,979 which describes a catheter fortemporary placement of an artificial heart valve.

Other percutaneous and endovascular cardiac repair procedures aredescribed in U.S. Pat. Nos. 4,917,089; 4,484,579; and 3,874,338; and PCTPublication No. WO 91/01689.

Thoracoscopic and other minimally invasive heart valve repair andreplacement procedures are described in U.S. Pat. Nos. 5,855,614;5,829,447; 5,823,956; 5,797,960; 5,769,812; and 5,718,725.

BRIEF SUMMARY OF THE INVENTION

The invention provides devices, systems and methods for tissueapproximation and repair at treatment sites. The devices, systems andmethods of the invention will find use in a variety of therapeuticprocedures, including endovascular, minimally-invasive, and opensurgical procedures, and can be used in various anatomical regions,including the abdomen, thorax, cardiovascular system, heart, intestinaltract, stomach, urinary tract, bladder, lung, and other organs, vessels,and tissues. The invention is particularly useful in those proceduresrequiring minimally-invasive or endovascular access to remote tissuelocations, where the instruments utilized must negotiate long, narrow,and tortuous pathways to the treatment site. In addition, many of thedevices and systems of the invention are adapted to be reversible andremovable from the patient at any point without interference with ortrauma to internal tissues.

In preferred embodiments, the devices, systems and methods of theinvention are adapted for fixation of tissue at a treatment site.Exemplary tissue fixation applications include cardiac valve repair,septal defect repair, vascular ligation and clamping, laceration repairand wound closure, but the invention may find use in a wide variety oftissue approximation and repair procedures. In a particularly preferredembodiment, the devices, systems and methods of the invention areadapted for repair of cardiac valves, and particularly the mitral valve,as a therapy for regurgitation. The invention enables two or more valveleaflets to be coapted using an “edge-to-edge” or “bow-tie” technique toreduce regurgitation, yet does not require open surgery through thechest and heart wall as in conventional approaches. Using the devices,systems and methods of the invention, the mitral valve can be accessedfrom a remote surgical or vascular access point and the two valveleaflets may be coapted using endovascular or minimally invasiveapproaches. While less preferred, in some circumstances the inventionmay also find application in open surgical approaches as well. Accordingto the invention, the mitral valve may be approached either from theatrial side (antegrade approach) or the ventricular side (retrogradeapproach), and either through blood vessels or through the heart wall.

The devices, systems and methods of the invention are centered onvariety of devices which may be used individually or in a variety ofcombinations to form interventional systems. In preferred embodiments,the interventional system includes a multi-catheter guiding system, adelivery catheter and an interventional device. Each of these componentswill be discussed herein.

In a first aspect of the present invention, a system for approximatingtissue comprises a delivery catheter having a lumen extendingtherethrough, an actuator rod having a proximal end and a distal end,and disposed at least partially in the lumen, and a flexible cablehaving a proximal end and a distal end. The flexible cable is at leastpartially disposed in the lumen. The proximal end of the flexible cableis coupled to the distal end of the actuator rod, and the flexible cableis resiliently biased to return to a substantially linear configurationafter being deflected 90° or more. The system also has a coupler coupledto the distal end of the flexible cable, and an implantable fixationdevice releasably attached to the coupler.

When rotated, the actuator rod may transmits a torque ranging from 0.25inch-ounces to 0.74 inch-ounces of torque with a substantially 1 to 1torque transmission ratio from the proximal end of the actuator rod tothe distal end of the actuator rod. The actuator rod may transmit atleast 1 pound of compressive force to the implantable fixation devicewithout substantial buckling of the rod. The actuator rod may alsowithstand at least 5 pounds of tensile force without substantialelongation of the rod.

The flexible cable may comprise a stranded cable which may comprise aplurality of wires wound in a helix. The flexible cable may comprise aninner core cable that may comprise a plurality of wires. At least halfof the torque applied to the proximal end of the flexible cable may betransmitted to the distal end thereof when the flexible cable is torquedin a first direction. Torque transmission in a second direction oppositethe first direction may be less efficient. Substantially all of thetorque may be transmitted from the proximal end to the distal end of theflexible cable. The flexible cable may comprise a plurality of wireswound in a first direction, and the flexible cable may transmit torquein the first direction with a higher torque transmission ratio than in asecond direction opposite the first direction.

The coupler may comprise a proximal bore and a distal bore. The distalend of the cable may be disposed in the proximal bore, and a portion ofthe fixation device may be disposed in the distal bore. The coupler maycomprise an enlarged proximal cylindrical portion and a smaller distalcylindrical portion. The enlarged proximal portion may be substantiallythe same diameter as the smaller distal cylindrical portion after theproximal portion has been swaged to the flexible cable. The coupler mayhave a first end and a second end opposite thereof. The first end of thecoupler may be swaged to the flexible cable, and the second end of thecoupler may be releasably attached to the fixation device. The first endof the coupler may be fixedly attached to the flexible cable, and thesecond end of the coupler may be releasably attached to the fixationdevice. The second end of the coupler may be threadably coupled to thefixation device.

The implantable fixation device may comprise a pair of fixation elementseach having a first end, a free end opposite the first end, and anengagement surface therebetween for engaging the tissue. The first endsmay be movably coupled together such that the fixation elements aremoveable between a closed position wherein the engagement surfaces faceeach other to an inverted position wherein the engagement surfaces faceaway from each other. The fixation device may also comprise an actuationmechanism coupled to the fixation elements and that is adapted to movethe fixation elements between the closed position and the invertedposition. The implantable fixation device further comprise a pair ofgripping elements. Each gripping element may be moveable with respect toone of the fixation elements and may be disposed in opposition to one ofthe engagement surfaces so as to capture tissue therebetween. Eachfixation element may be at least partially concave and each grippingelement may be at least partially recessed within the fixation elementin a deployed configuration.

The system may further comprise a sleeve that may join the proximal endof the flexible cable with the distal end of the elongate shaft. Thesleeve may be fixedly attached to the flexible cable and the elongateshaft. The sleeve may comprise a central bore therethrough, and theproximal end of the flexible cable and the distal end of the elongateshaft may be disposed in the central bore. The sleeve may be swaged toboth the flexible cable and the elongate shaft.

Other aspects of the nature and advantages of the invention are setforth in the detailed description set forth below, taken in conjunctionwith the drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates the left ventricle and left atrium of the heartduring systole.

FIG. 2A illustrates free edges of leaflets in normal coaptation, andFIG. 2B illustrates the free edges in regurgitative coaptation.

FIGS. 3A-3C illustrate grasping of the leaflets with a fixation device,inversion of the distal elements of the fixation device and removal ofthe fixation device, respectively.

FIG. 4 illustrates the position of the fixation device in a desiredorientation relative to the leaflets.

FIGS. 5A-5B and 6A-6B illustrate exemplary embodiments of couplingmechanisms of the instant application.

FIG. 7 illustrates another embodiment of the fixation device of thepresent invention.

FIGS. 8A-8B, 9A-9B, 10A-10B, 11A-11B, and 12-14 illustrate embodimentsof a fixation device in various possible positions during introductionand placement of the device within the body to perform a therapeuticprocedure.

FIGS. 15A-15C illustrate a covering on the fixation device wherein thedevice is in various positions.

FIG. 16 provides a cross-sectional view of a locking mechanism.

FIGS. 17-18 provide a cross-sectional view of the locking mechanism inthe unlocked and locked positions respectively.

FIG. 19 is a perspective view of an embodiment of a delivery catheterfor a fixation device.

FIG. 20 illustrates an embodiment of a fixation device coupled to thedistal end of a delivery catheter.

FIG. 21 illustrates a portion of the shaft of a delivery catheter and afixation device which is coupleable with the catheter.

FIGS. 22A-22B illustrate an exemplary embodiment of an actuator rodassembly.

FIGS. 23A-23B, 24A-24B, 25A-25B, and 26A-26B illustrate layers of anexemplary cable used in the actuator rod of FIGS. 22A-22B.

FIGS. 27A-27B, 28A-28B, 29A-29B, 30A-30B, and 31A-31B illustrate layersin another exemplary cable used in the actuator rod of FIGS. 22A-22B.

FIGS. 32-34 are cross-sectional views of embodiments of the shaft of thedelivery catheter.

FIGS. 34A-34B illustrate embodiments of the nose of the shaft of thedelivery catheter.

FIG. 35A illustrates various arrangements of lock lines engaging releaseharnesses of a locking mechanism.

FIG. 36A illustrates various arrangements of proximal element linesengaging proximal elements of a fixation device.

FIG. 37 illustrates an embodiment of the handle of the deliverycatheter.

FIG. 38 is a cross-sectional view of the main body of the handle.

FIG. 39 illustrates an embodiment of a lock line handle.

FIG. 39A illustrates the lock line handle of FIG. 39 positioned within asemi-tube which is disposed within the sealed chamber.

FIGS. 40A-40B illustrate a mechanism for applying tension to lock lines.

FIGS. 41 and 41A-41B illustrate features of the actuator rod control andhandle.

FIG. 42 is a perspective view of an embodiment of a multi-catheterguiding system of the present invention, and an interventional catheterpositioned therethrough.

FIG. 43A illustrates a primary curvature in an outer guide catheter.

FIG. 43B illustrates a secondary curvature in an inner guide catheter.

FIGS. 43C-43D illustrate example movement of an inner guide catheterthrough angle thetas.

FIG. 44A is a perspective side view of a multi-catheter guiding systemhaving an additional curve in the outer guide catheter.

FIG. 44B illustrates lifting of the outer guide catheter due to theadditional curve of FIG. 44A.

FIGS. 45A-45D illustrate a method of using the multi-catheter guidingsystem for accessing the mitral valve.

FIGS. 46A-46D illustrate curvature of a guide catheter of the presentinvention by the actuation of one or more pullwires.

FIG. 46E illustrates attachment of a pullwire to a tip ring.

FIGS. 47A-47I illustrate embodiments of the present invention comprisingsections constructed with the inclusion of braiding or a coil.

FIGS. 48A-48C illustrate a keying feature of the present invention.

FIGS. 49A-49B are perspective views of a guide catheter including aseries of articulating members.

FIG. 50 illustrates embodiments of the handles.

FIG. 51 illustrates the handles of FIG. 50 with a portion of the housingremoved.

FIG. 52 illustrates steering mechanisms within a handle.

FIG. 53 illustrates attachment of a pullwire to a disk.

FIGS. 54A-54B illustrate a hard stop peg restricting rotation of a disk.

FIGS. 55A-55C illustrates a portion of a hard stop gear assembly.

FIGS. 56A-56F illustrate a ball restricting rotation of a disk.

FIG. 57 illustrates an embodiment of a friction assembly.

FIG. 58 illustrates an embodiment of an interventional system of thepresent invention.

FIG. 58A illustrates an embodiment of a hemostatic valve for use withthe present invention.

FIG. 58B illustrates an embodiment of a fixation device introducer.

FIG. 59 illustrates another embodiment of an interventional system ofthe present invention.

FIGS. 60-62 illustrate an embodiment of a stabilizer base for use withthe present invention.

FIG. 63 illustrates a kit constructed in accordance with the principlesof the present invention

DETAILED DESCRIPTION OF THE INVENTION I. Cardiac Physiology

The left ventricle LV of a normal heart H in systole is illustrated inFIG. 1. The left ventricle LV is contracting and blood flows outwardlythrough the tricuspid (aortic) valve AV in the direction of the arrows.Back flow of blood or “regurgitation” through the mitral valve MV isprevented since the mitral valve is configured as a “check valve” whichprevents back flow when pressure in the left ventricle is higher thanthat in the left atrium LA. The mitral valve MV comprises a pair ofleaflets having free edges FE which meet evenly to close, as illustratedin FIG. 1. The opposite ends of the leaflets LF are attached to thesurrounding heart structure along an annular region referred to as theannulus AN. The free edges FE of the leaflets LF are secured to thelower portions of the left ventricle LV through chordae tendinae CT(referred to hereinafter as the chordae) which include plurality ofbranching tendons secured over the lower surfaces of each of the valveleaflets LF. The chordae CT in turn, are attached to the papillarymuscles PM which extend upwardly from the lower portions of the leftventricle and intraventricular septum IVS.

A number of structural defects in the heart can cause mitral valveregurgitation. Regurgitation occurs when the valve leaflets do not closeproperly allowing leakage from the ventricle into the atrium. As shownin FIG. 2A, the free edges of the anterior and posterior leafletsnormally meet along a line of coaptation C. An example of a defectcausing regurgitation is shown in FIG. 2B. Here an enlargement of theheart causes the mitral annulus to become enlarged, making it impossiblefor the free edges FE to meet during systole. This results in a gap Gwhich allows blood to leak through the valve during ventricular systole.Ruptured or elongated chordae can also cause a valve leaflet to prolapsesince inadequate tension is transmitted to the leaflet via the chordae.While the other leaflet maintains a normal profile, the two valveleaflets do not properly meet and leakage from the left ventricle intothe left atrium will occur. Such regurgitation can also occur inpatients who have suffered ischemic heart disease where the leftventricle does not contract sufficiently to effect proper closure.

II. General Overview

The present invention provides methods and devices for grasping,approximating and fixating tissues such as valve leaflets to treatcardiac valve regurgitation, particularly mitral valve regurgitation.The present invention also provides features that allow repositioningand removal of the device if so desired, particularly in areas whereremoval may be hindered by anatomical features such as chordae CT. Suchremoval would allow the surgeon to reapproach the valve in a new mannerif so desired.

Grasping will preferably be atraumatic providing a number of benefits.By atraumatic, it is meant that the devices and methods of the inventionmay be applied to the valve leaflets and then removed without causingany significant clinical impairment of leaflet structure or function.The leaflets and valve continue to function substantially the same asbefore the invention was applied. Thus, some minor penetration ordenting of the leaflets may occur using the invention while stillmeeting the definition of “atraumatic.” This enables the devices of theinvention to be applied to a diseased valve and, if desired, removed orrepositioned without having negatively affected valve function. Inaddition, it will be understood that in some cases it may be necessaryor desirable to pierce or otherwise permanently affect the leafletsduring either grasping, fixing or both. In some of these cases, graspingand fixation may be accomplished by a single device. Although a numberof embodiments are provided to achieve these results, a general overviewof the basic features will be presented herein. Such features are notintended to limit the scope of the invention and are presented with theaim of providing a basis for descriptions of individual embodimentspresented later in the application.

The devices and methods of the invention rely upon the use of aninterventional tool that is positioned near a desired treatment site andused to grasp the target tissue. In endovascular applications, theinterventional tool is typically an interventional catheter. In surgicalapplications, the interventional tool is typically an interventionalinstrument. In preferred embodiments, fixation of the grasped tissue isaccomplished by maintaining grasping with a portion of theinterventional tool which is left behind as an implant. While theinvention may have a variety of applications for tissue approximationand fixation throughout the body, it is particularly well adapted forthe repair of valves, especially cardiac valves such as the mitralvalve. Referring to FIG. 3A, an interventional tool 10, having adelivery device, such as a shaft 12, and a fixation device 14, isillustrated having approached the mitral valve MV from the atrial sideand grasped the leaflets LF. The mitral valve may be accessed eithersurgically or by using endovascular techniques, and either by aretrograde approach through the ventricle or by an antegrade approachthrough the atrium, as described above. For illustration purposes, anantegrade approach is described.

The fixation device 14 is releasably attached to the shaft 12 of theinterventional tool 10 at its distal end. When describing the devices ofthe invention herein, “proximal” shall mean the direction toward the endof the device to be manipulated by the user outside the patient's body,and “distal” shall mean the direction toward the working end of thedevice that is positioned at the treatment site and away from the user.With respect to the mitral valve, proximal shall refer to the atrial orupstream side of the valve leaflets and distal shall refer to theventricular or downstream side of the valve leaflets.

The fixation device 14 typically comprises proximal elements 16 (orgripping elements) and distal elements 18 (or fixation elements) whichprotrude radially outward and are positionable on opposite sides of theleaflets LF as shown so as to capture or retain the leafletstherebetween. The proximal elements 16 are preferably comprised ofcobalt chromium, nitinol or stainless steel, and the distal elements 18are preferably comprised of cobalt chromium or stainless steel, howeverany suitable materials may be used. The fixation device 14 is coupleableto the shaft 12 by a coupling mechanism 17. The coupling mechanism 17allows the fixation device 14 to detach and be left behind as an implantto hold the leaflets together in the coapted position.

In some situations, it may be desired to reposition or remove thefixation device 14 after the proximal elements 16, distal elements 18,or both have been deployed to capture the leaflets LF. Suchrepositioning or removal may be desired for a variety of reasons, suchas to reapproach the valve in an attempt to achieve better valvefunction, more optimal positioning of the device 14 on the leaflets,better purchase on the leaflets, to detangle the device 14 fromsurrounding tissue such as chordae, to exchange the device 14 with onehaving a different design, or to abort the fixation procedure, to name afew. To facilitate repositioning or removal of the fixation device 14the distal elements 18 are releasable and optionally invertible to aconfiguration suitable for withdrawal of the device 14 from the valvewithout tangling or interfering with or damaging the chordae, leafletsor other tissue. FIG. 3B illustrates inversion wherein the distalelements 18 are moveable in the direction of arrows 40 to an invertedposition. Likewise, the proximal elements 16 may be raised, if desired.In the inverted position, the device 14 may be repositioned to a desiredorientation wherein the distal elements may then be reverted to agrasping position against the leaflets as in FIG. 3A. Alternatively, thefixation device 14 may be withdrawn (indicated by arrow 42) from theleaflets as shown in FIG. 3C. Such inversion reduces trauma to theleaflets and minimizes any entanglement of the device with surroundingtissues. Once the device 14 has been withdrawn through the valveleaflets, the proximal and distal elements may be moved to a closedposition or configuration suitable for removal from the body or forreinsertion through the mitral valve.

FIG. 4 illustrates the position of the fixation device 14 in a desiredorientation in relation to the leaflets LF. This is a short-axis view ofthe mitral valve MV from the atrial side, therefore, the proximalelements 16 are shown in solid line and the distal elements 18 are shownin dashed line. The proximal and distal elements 16, 18 are positionedto be substantially perpendicular to the line of coaptation C. Thedevice 14 may be moved roughly along the line of coaptation to thelocation of regurgitation. The leaflets LF are held in place so thatduring diastole, as shown in FIG. 4, the leaflets LF remain in positionbetween the elements 16, 18 surrounded by openings O which result fromthe diastolic pressure gradient. Advantageously, leaflets LF are coaptedsuch that their proximal or upstream surfaces are facing each other in avertical orientation, parallel to the direction of blood flow throughmitral valve MV. The upstream surfaces may be brought together so as tobe in contact with one another or may be held slightly apart, but willpreferably be maintained in the vertical orientation in which theupstream surfaces face each other at the point of coaptation. Thissimulates the double orifice geometry of a standard surgical bow-tierepair. Color Doppler echo will show if the regurgitation of the valvehas been reduced. If the resulting mitral flow pattern is satisfactory,the leaflets may be fixed together in this orientation. If the resultingcolor Doppler image shows insufficient improvement in mitralregurgitation, the interventional tool 10 may be repositioned. This maybe repeated until an optimal result is produced wherein the leaflets LFare held in place.

Once the leaflets are coapted in the desired arrangement, the fixationdevice 14 is then detached from the shaft 12 and left behind as animplant to hold the leaflets together in the coapted position. Asmentioned previously, the fixation device 14 is coupled to the shaft 12by a coupling mechanism 17. FIGS. 5A-5B, 6A-6B illustrate exemplaryembodiments of such coupling mechanisms. FIG. 5A shows an upper shaft 20and a detachable lower shaft 22 which are interlocked at a joining lineor mating surface 24. The mating surface 24 may have any shape orcurvature which will allow or facilitate interlocking and laterdetachment. A snuggly fitting outer sheath 26 is positioned over theshafts 20, 22 to cover the mating surface 24 as shown. FIG. 5Billustrates detachment of the lower shaft 22 from the upper shaft 20.This is achieved by retracting the outer sheath 26, so that the matingsurface 24 is exposed, which allows the shafts 20, 22 to separate.

Similarly, FIG. 6A illustrates a tubular upper shaft 28 and a detachabletubular lower shaft 30 which are interlocked at a mating surface 32.Again, the mating surface 32 may have any shape or curvature which willallow or facilitate interlocking and later detachment. The tubular uppershaft 28 and tubular lower shaft 30 form an outer member having an axialchannel. A snuggly fitting rod 34 or inner member is inserted throughthe tubular shafts 28, 30 to bridge the mating surface 32 as shown. Therod 34 may also be used to actuate the fixation device, such as actuatorrod 64 seen in FIG. 21 or actuator rod 64 a illustrated in FIGS.22A-22B, described below. FIG. 6B illustrates detachment of the lowershaft 30 from the upper shaft 28. This is achieved by retracting the rod34 to a position above the mating surface 32 which in turn allows theshafts 28, 30 to separate. Other examples of coupling mechanisms aredescribed and illustrated in U.S. Pat. No. 6,752,813 (Attorney DocketNo. 020489-000400), and U.S. Patent Publication No. 2009/0163934(Attorney Docket No. 020489-001470US), the entire contents of each ofwhich are incorporated herein by reference for all purposes.

In a preferred embodiment, mating surface 24 (or mating surface 32) is asigmoid curve defining a male element and female element on upper shaft20 (or upper shaft 28) which interlock respectively with correspondingfemale and male elements on lower shaft 22 (or lower shaft 30).Typically, the lower shaft is the coupling mechanism 17 of the fixationdevice 14. Therefore, the shape of the mating surface selected willpreferably provide at least some mating surfaces transverse to the axialaxis of the a mechanism 19 to facilitate application of compressive andtensile forces through the coupling mechanism 17 to the fixation device14, yet causing minimal interference when the fixation device 14 is tobe released from the upper shaft.

III. Fixation Device

A. Introduction and Placement of Fixation Device

The fixation device 14 is delivered to the valve or the desired tissueswith the use of a delivery device. The delivery device may be rigid orflexible depending on the application. For endovascular applications,the delivery device comprises a flexible delivery catheter which will bedescribed in later sections. Typically, however, such a cathetercomprises a shaft, having a proximal end and a distal end, and afixation device releasably attached to its distal end. The shaft isusually elongate and flexible, suitable for intravascular introduction.Alternatively, the delivery device may comprise a shorter and lessflexible interventional instrument which may be used for trans-thoracicsurgical introduction through the wall of the heart, although someflexibility and a minimal profile will generally be desirable. Afixation device is releasably coupleable with the delivery device asillustrated in FIG. 3A. The fixation device may have a variety of forms,a few embodiments of which will be described herein.

FIG. 7 illustrates another embodiment of a fixation device 14. Here, thefixation device 14 is shown coupled to a shaft 12 to form aninterventional tool 10. The fixation device 14 includes a couplingmember 19 and a pair of opposed distal elements 18. The distal elements18 comprise elongate arms 53, each arm having a proximal end 52rotatably connected to the coupling member 19 and a free end 54. Thefree ends 54 have a rounded shape to minimize interference with andtrauma to surrounding tissue structures. Preferably, each free end 54defines a curvature about two axes, one being an axis 66 perpendicularto longitudinal axis of arms 53. Thus, the engagement surfaces 50 have acupped or concave shape to surface area in contact with tissue and toassist in grasping and holding the valve leaflets. This further allowsarms 53 to nest around the shaft 12 in the closed position to minimizethe profile of the device. Preferably, arms 53 are at least partiallycupped or curved inwardly about their longitudinal axes 66. Also,preferably, each free end 54 defines a curvature about an axis 67perpendicular to axis 66 or the longitudinal axis of arms 53. Thiscurvature is a reverse curvature along the most distal portion of thefree end 54. Likewise, the longitudinal edges of the free ends 54 mayflare outwardly. Both the reverse curvature and flaring minimize traumato the tissue engaged therewith.

In a preferred embodiment suitable for mitral valve repair, thetransverse width across engagement surfaces 50 (which determines thewidth of tissue engaged) is at least about 2 mm, usually 3-10 mm, andpreferably about 4-6 mm. In some situations, a wider engagement isdesired wherein the engagement surfaces 50 are larger, for example about2 cm, or multiple fixation devices are used adjacent to each other. Arms53 and engagement surfaces 50 are configured to engage a length oftissue of about 4-10 mm, and preferably about 6-8 mm along thelongitudinal axis of arms 53. Arms 53 further include a plurality ofopenings to enhance grip and to promote tissue ingrowth followingimplantation.

The valve leaflets are grasped between the distal elements 18 andproximal elements 16. In some embodiments, the proximal elements 16 areflexible, resilient, and cantilevered from coupling member 19. Theproximal elements are preferably resiliently biased toward the distalelements. Each proximal element 16 is shaped and positioned to be atleast partially recessed within the concavity of the distal element 18when no tissue is present. When the fixation device 14 is in the openposition, the proximal elements 16 are shaped such that each proximalelement 16 is separated from the engagement surface 50 near the proximalend 52 of arm 53 and slopes toward the engagement surface 50 near thefree end 54 with the free end of the proximal element contactingengagement surface 50, as illustrated in FIG. 7. This shape of theproximal elements 16 accommodates valve leaflets or other tissues ofvarying thicknesses.

Proximal elements 16 include a plurality of openings 63 and scallopedside edges 61 to increase grip on tissue. The proximal elements 16optionally include frictional accessories, frictional features orgrip-enhancing elements to assist in grasping and/or holding theleaflets. In preferred embodiments, the frictional accessories comprisebarbs 60 having tapering pointed tips extending toward engagementsurfaces 50. It may be appreciated that any suitable frictionalaccessories may be used, such as prongs, windings, bands, barbs,grooves, channels, bumps, surface roughening, sintering, high-frictionpads, coverings, coatings or a combination of these. Optionally, magnetsmay be present in the proximal and/or distal elements. It may beappreciated that the mating surfaces will be made from or will includematerial of opposite magnetic charge to cause attraction by magneticforce. For example, the proximal elements and distal elements may eachinclude magnetic material of opposite charge so that tissue is heldunder constant compression between the proximal and distal elements tofacilitate faster healing and ingrowth of tissue. Also, the magneticforce may be used to draw the proximal elements 16 toward the distalelements 18, in addition to or alternatively to biasing of the proximalelements toward the distal elements. This may assist in deployment ofthe proximal elements 16. In another example, the distal elements 18each include magnetic material of opposite charge so that tissuepositioned between the distal elements 18 is held therebetween bymagnetic force.

The proximal elements 16 may be covered with a fabric or other flexiblematerial as described below to enhance grip and tissue ingrowthfollowing implantation. Preferably, when fabrics or coverings are usedin combination with barbs or other frictional features, such featureswill protrude through such fabric or other covering so as to contact anytissue engaged by proximal elements 16.

In an exemplary embodiment, proximal elements 16 are formed frommetallic sheet of a spring-like material using a stamping operationwhich creates openings 63, scalloped edges 61 and barbs 60.Alternatively, proximal elements 16 could be comprised of a spring-likematerial or molded from a biocompatible polymer. It should be noted thatwhile some types of frictional accessories that can be used in thepresent invention may permanently alter or cause some trauma to thetissue engaged thereby, in a preferred embodiment, the frictionalaccessories will be atraumatic and will not injure or otherwise affectthe tissue in a clinically significant way. For example, in the case ofbarbs 60, it has been demonstrated that following engagement of mitralvalve leaflets by fixation device 14, should the device later be removedduring the procedure barbs 60 leave no significant permanent scarring orother impairment of the leaflet tissue and are thus consideredatraumatic.

The fixation device 14 also includes an actuation mechanism 58. In thisembodiment, the actuation mechanism 58 comprises two link members orlegs 68, each leg 68 having a first end 70 which is rotatably joinedwith one of the distal elements 18 at a riveted joint 76 and a secondend 72 which is rotatably joined with a stud 74. The legs 68 arepreferably comprised of a rigid or semi-rigid metal or polymer such asElgiloy®, cobalt chromium or stainless steel, however any suitablematerial may be used. While in the embodiment illustrated both legs 68are pinned to stud 74 by a single rivet 78, it may be appreciated,however, that each leg 68 may be individually attached to the stud 74 bya separate rivet or pin. The stud 74 is joinable with an actuator rod 64(not shown) which extends through the shaft 12 and is axially extendableand retractable to move the stud 74 and therefore the legs 68 whichrotate the distal elements 18 between closed, open and invertedpositions. Likewise, immobilization of the stud 74 holds the legs 68 inplace and therefore holds the distal elements 18 in a desired position.The stud 74 may also be locked in place by a locking feature which willbe further described in later sections.

In any of the embodiments of fixation device 14 disclosed herein, it maybe desirable to provide some mobility or flexibility in distal elements18 and/or proximal elements 16 in the closed position to enable theseelements to move or flex with the opening or closing of the valveleaflets. This provides shock absorption and thereby reduces force onthe leaflets and minimizes the possibility for tearing or other traumato the leaflets. Such mobility or flexibility may be provided by using aflexible, resilient metal or polymer of appropriate thickness toconstruct the distal elements 18. Also, the locking mechanism of thefixation device (described below) may be constructed of flexiblematerials to allow some slight movement of the proximal and distalelements even when locked. Further, the distal elements 18 can beconnected to the coupling mechanism 19 or to actuation mechanism 58 by amechanism that biases the distal element into the closed position(inwardly) but permits the arms to open slightly in response to forcesexerted by the leaflets. For example, rather than being pinned at asingle point, these components may be pinned through a slot that alloweda small amount of translation of the pin in response to forces againstthe arms. A spring is used to bias the pinned component toward one endof the slot.

FIGS. 8A-8B, 9A-9B, 10A-10B, 11A-11B, and FIGS. 12-14 illustrateembodiments of the fixation device 14 of FIG. 7 in various possiblepositions during introduction and placement of the device 14 within thebody to perform a therapeutic procedure. FIG. 8A illustrates anembodiment of an interventional tool 10 delivered through a catheter 86.It may be appreciated that the interventional tool 10 may take the formof a catheter, and likewise, the catheter 86 may take the form of aguide catheter or sheath. However, in this example the termsinterventional tool 10 and catheter 86 will be used. The interventionaltool 10 comprises a fixation device 14 coupled to a shaft 12 and thefixation device 14 is shown in the closed position. FIG. 8B illustratesa similar embodiment of the fixation device of FIG. 8A in a larger view.In the closed position, the opposed pair of distal elements 18 arepositioned so that the engagement surfaces 50 face each other. Eachdistal element 18 comprises an elongate arm 53 having a cupped orconcave shape so that together the arms 53 surround the shaft 12 andoptionally contact each other on opposite sides of the shaft. Thisprovides a low profile for the fixation device 14 which is readilypassable through the catheter 86 and through any anatomical structures,such as the mitral valve. In addition, FIG. 8B further includes anactuation mechanism 58. In this embodiment, the actuation mechanism 58comprises two legs 68 which are each movably coupled to a base 69. Thebase 69 is joined with an actuator rod 64 which extends through theshaft 12 and is used to manipulate the fixation device 14. In someembodiments, the actuator rod 64 attaches directly to the actuationmechanism 58, particularly the base 69. However, the actuator rod 64 mayalternatively attach to a stud 74 which in turn is attached to the base69. In some embodiments, the stud 74 is threaded so that the actuatorrod 64 attaches to the stud 74 by a screw-type action. However, the rod64 and stud 74 may be joined by any mechanism which is releasable toallow the fixation device 14 to be detached from shaft 12. Other aspectsof the actuator rod and its coupling with the fixation device aredisclosed below.

FIGS. 9A-9B illustrate the fixation device 14 in the open position. Inthe open position, the distal elements 18 are rotated so that theengagement surfaces 50 face a first direction. Distal advancement of thestud 74 relative to coupling member 19 by action of the actuator rod 64applies force to the distal elements 18 which begin to rotate aroundjoints 76 due to freedom of movement in this direction. Such rotationand movement of the distal elements 18 radially outward causes rotationof the legs 68 about joints 80 so that the legs 68 are directed slightlyoutwards. The stud 74 may be advanced to any desired distancecorrelating to a desired separation of the distal elements 18. In theopen position, engagement surfaces 50 are disposed at an acute anglerelative to shaft 12, and are preferably at an angle of between 90 and180 degrees relative to each other. In one embodiment, in the openposition the free ends 54 of arms 53 have a span therebetween of about10-20 mm, usually about 12-18 mm, and preferably about 14-16 mm.

Proximal elements 16 are typically biased outwardly toward arms 53. Theproximal elements 16 may be moved inwardly toward the shaft 12 and heldagainst the shaft 12 with the aid of proximal element lines 90 which canbe in the form of sutures, wires, nitinol wire, rods, cables, polymericlines, or other suitable structures. The proximal element lines 90 maybe connected with the proximal elements 16 by threading the lines 90 ina variety of ways. When the proximal elements 16 have a loop shape, asshown in FIG. 9A, the line 90 may pass through the loop and double back.When the proximal elements 16 have an elongate solid shape, as shown inFIG. 9B, the line 90 may pass through one or more of the openings 63 inthe element 16. Further, a line loop 48 may be present on a proximalelement 16, also illustrated in FIG. 9B, through which a proximalelement line 90 may pass and double back. Such a line loop 48 may beuseful to reduce friction on proximal element line 90 or when theproximal elements 16 are solid or devoid of other loops or openingsthrough which the proximal element lines 90 may attach. A proximalelement line 90 may attach to the proximal elements 16 by detachablemeans which would allow a single line 90 to be attached to a proximalelement 16 without doubling back and would allow the single line 90 tobe detached directly from the proximal element 16 when desired. Examplesof such detachable means include hooks, snares, clips or breakablecouplings, to name a few. By applying sufficient tension to the proximalelement line 90, the detachable means may be detached from the proximalelement 16 such as by breakage of the coupling. Other mechanisms fordetachment may also be used. Similarly, a lock line 92 may be attachedand detached from a locking mechanism by similar detachable means.

In the open position, the fixation device 14 can engage the tissue whichis to be approximated or treated. The embodiment illustrated in FIGS.7-9B is adapted for repair of the mitral valve using an antegradeapproach from the left atrium. The interventional tool 10 is advancedthrough the mitral valve from the left atrium to the left ventricle. Thedistal elements 18 are oriented to be perpendicular to the line ofcoaptation and then positioned so that the engagement surfaces 50contact the ventricular surface of the valve leaflets, thereby graspingthe leaflets. The proximal elements 16 remain on the atrial side of thevalve leaflets so that the leaflets lie between the proximal and distalelements. In this embodiment, the proximal elements 16 have frictionalaccessories, such as barbs 60 which are directed toward the distalelements 18. However, neither the proximal elements 16 nor the barbs 60contact the leaflets at this time.

The interventional tool 10 may be repeatedly manipulated to repositionthe fixation device 14 so that the leaflets are properly contacted orgrasped at a desired location. Repositioning is achieved with thefixation device in the open position. In some instances, regurgitationmay also be checked while the device 14 is in the open position. Ifregurgitation is not satisfactorily reduced, the device may berepositioned and regurgitation checked again until the desired resultsare achieved.

It may also be desired to invert the fixation device 14 to aid inrepositioning or removal of the fixation device 14. FIGS. 10A-10Billustrate the fixation device 14 in the inverted position. By furtheradvancement of stud 74 relative to coupling member 19, the distalelements 18 are further rotated so that the engagement surfaces 50 faceoutwardly and free ends 54 point distally, with each arm 53 forming anobtuse angle relative to shaft 12. The angle between arms 53 ispreferably in the range of about 270 to 360 degrees. Further advancementof the stud 74 further rotates the distal elements 18 around joints 76.This rotation and movement of the distal elements 18 radially outwardcauses rotation of the legs 68 about joints 80 so that the legs 68 arereturned toward their initial position, generally parallel to eachother. The stud 74 may be advanced to any desired distance correlatingto a desired inversion of the distal elements 18. Preferably, in thefully inverted position, the span between free ends 54 is no more thanabout 20 mm, usually less than about 16 mm, and preferably about 12-14mm. In this illustration, the proximal elements 16 remain positionedagainst the shaft 12 by exerting tension on the proximal element lines90. Thus, a relatively large space may be created between the elements16, 18 for repositioning. In addition, the inverted position allowswithdrawal of the fixation device 14 through the valve while minimizingtrauma to the leaflets. Engagement surfaces 50 provide an atraumaticsurface for deflecting tissue as the fixation device is refractedproximally. It should be further noted that barbs 60 are angled slightlyin the distal direction (away from the free ends of the proximalelements 16), reducing the risk that the barbs will catch on or laceratetissue as the fixation device is withdrawn.

Once the fixation device 14 has been positioned in a desired locationagainst the valve leaflets, the leaflets may then be captured betweenthe proximal elements 16 and the distal elements 18. FIGS. 11A-11Billustrate the fixation device 14 in such a position. Here, the proximalelements 16 are lowered toward the engagement surfaces 50 so that theleaflets are held therebetween. In FIG. 11B, the proximal elements 16are shown to include barbs 60 which may be used to provide atraumaticgripping of the leaflets. Alternatively, larger, more sharply pointedbarbs or other penetration structures may be used to pierce the leafletsto more actively assist in holding them in place. This position issimilar to the open position of FIGS. 9A-9B, however the proximalelements 16 are now lowered toward arms 53 by releasing tension onproximal element lines 90 to compress the leaflet tissue therebetween.At any time, the proximal elements 16 may be raised and the distalelements 18 adjusted or inverted to reposition the fixation device 14,if regurgitation is not sufficiently reduced.

After the leaflets have been captured between the proximal and distalelements 16, 18 in a desired arrangement, the distal elements 18 may belocked to hold the leaflets in this position or the fixation device 14may be returned to or toward a closed position. Such locking will bedescribed in a later section. FIG. 12 illustrates the fixation device 14in the closed position wherein the leaflets (not shown) are captured andcoapted. This is achieved by retraction of the stud 74 proximallyrelative to coupling member 19 so that the legs 68 of the actuationmechanism 58 apply an upwards force to the distal elements 18 which inturn rotate the distal elements 18 so that the engagement surfaces 50again face one another. The released proximal elements 16 which arebiased outwardly toward distal elements 18 are concurrently urgedinwardly by the distal elements 18. The fixation device 14 may then belocked to hold the leaflets in this closed position as described below.

As shown in FIG. 13, the fixation device 14 may then be released fromthe shaft 12. As mentioned, the fixation device 14 is releasablycoupleable to the shaft 12 by coupling member 19 (best seen in FIG. 14).FIG. 13 illustrates the coupling structure, a portion of the shaft 12 towhich the coupling member 19 of the fixation device 14 attaches. Asshown, the proximal element lines 90 may remain attached to the proximalelements 16 following detachment from shaft 12 to function as a tetherto keep the fixation device 14 connected with the catheter 86.Optionally, a separate tether coupled between shaft 12 and fixationdevice 14 may be used expressly for this purpose while the proximalelement lines 90 are removed. In any case, the repair of the leaflets ortissue may be observed by non-invasive visualization techniques, such asechocardiography, to ensure the desired outcome. If the repair is notdesired, the fixation device 14 may be retrieved with the use of thetether or proximal element lines 90 so as to reconnect coupling member19 with shaft 12.

In an exemplary embodiments, proximal element lines 90 are elongatedflexible threads, wire, cable, sutures or lines extending through shaft12, looped through proximal elements 16, and extending back throughshaft 12 to its proximal end. When detachment is desired, one end ofeach line may be released at the proximal end of the shaft 12 and theother end pulled to draw the free end of the line distally through shaft12 and through proximal element 16 thereby releasing the fixationdevice.

FIG. 14 illustrates a released fixation device 14 in a closed position.As shown, the coupling member 19 remains separated from the shaft 12 ofthe interventional tool 10 and the proximal elements 16 are deployed sothat tissue (not shown) may reside between the proximal elements 16 anddistal elements 18.

While the above described embodiments of the invention utilize apush-to-open, pull-to-close mechanism for opening and closing distalelements 18, it should be understood that a pull-to-open, push-to-closemechanism is equally possible. For example, distal elements 18 may becoupled at their proximal ends to stud 74 rather than to coupling member19, and legs 68 may be coupled at their proximal ends to coupling member19 rather than to stud 74. In this example, when stud 74 is pusheddistally relative to coupling member 19, distal elements 18 would close,while pulling on stud 74 proximally toward coupling member 19 would opendistal elements 18.

B. Covering on Fixation Device

The fixation device 14 may optionally include a covering. The coveringmay assist in grasping the tissue and may later provide a surface fortissue ingrowth. Ingrowth of the surrounding tissues, such as the valveleaflets, provides stability to the device 14 as it is further anchoredin place and may cover the device with native tissue thus reducing thepossibility of immunologic reactions. The covering may be comprised ofany biocompatible material, such as polyethylene terepthalate,polyester, cotton, polyurethane, expanded polytetrafluoroethylene(ePTFE), silicon, or various polymers or fibers and have any suitableform, such as a fabric, mesh, textured weave, felt, looped or porousstructure. Generally, the covering has a low profile so as not tointerfere with delivery through an introducer sheath or with graspingand coapting of leaflets or tissue.

FIGS. 15A-15C illustrate a covering 100 on the fixation device 14wherein the device 14 is in various positions. FIG. 15A shows thecovering 100 encapsulating the distal elements 18 and the actuationmechanism 58 while the device 14 is in the open position. Thus, theengagement surfaces 50 are covered by the covering 100 which helps tominimize trauma on tissues and provides additional friction to assist ingrasping and retaining tissues. FIG. 15B shows the device 14 of FIG. 15Ain the inverted position. The covering 100 is loosely fitted and/or isflexible or elastic such that the device 14 can freely move to variouspositions and the covering 100 conforms to the contours of the device 14and remains securely attached in all positions. FIG. 15C shows thedevice 14 in the closed position. Thus, when the fixation device 14 isleft behind as an implant in the closed position, the exposed surfacesof the device 14 are substantially covered by the covering 100. It maybe appreciated that the covering 100 may cover specific parts of thefixation device 14 while leaving other parts exposed. For example, thecovering 100 may comprise sleeves that fit over the distal elements 18and not the actuation mechanism 58, caps that fit over the distal ends54 of the distal elements 18 or pads that cover the engagement surfaces50, to name a few. It may be appreciated that, the covering 100 mayallow any frictional accessories, such as barbs, to be exposed. Also,the covering 100 may cover the proximal elements 16 and/or any othersurfaces of the fixation device 14. In any case, the covering 100 shouldbe durable to withstand multiple introduction cycles and, when implantedwithin a heart, a lifetime of cardiac cycles.

The covering 100 may alternatively be comprised of a polymer or othersuitable materials dipped, sprayed, coated or otherwise adhered to thesurfaces of the fixation device 14. Optionally, the polymer coating mayinclude pores or contours to assist in grasping the tissue and/or topromote tissue ingrowth.

Any of the coverings 100 may optionally include drugs, antibiotics,anti-thrombosis agents, or anti-platelet agents such as heparin,COUMADIN® (Warfarin Sodium), to name a few. These agents may, forexample, be impregnated in or coated on the coverings 100. These agentsmay then be delivered to the grasped tissues surrounding tissues and/orbloodstream for therapeutic effects.

C. Fixation Device Locking Mechanisms

As mentioned previously, the fixation device 14 optionally includes alocking mechanism for locking the device 14 in a particular position,such as an open, closed or inverted position or any positiontherebetween. It may be appreciated that the locking mechanism includesan unlocking mechanism which allows the device to be both locked andunlocked. FIGS. 16-18 illustrate an exemplary embodiment of a lockingmechanism 106.

FIG. 16 provides a front view of a locking mechanism embodiment. Herethe proximal elements 16 are supported by a single proximal element line90 which is through both of the proximal elements 16. In thisarrangement both of the elements are raised and lowered simultaneouslyby action of a single proximal element line 90. Whether the proximalelements 16 are manipulated individually by separate proximal elementlines 90 or jointly by a single proximal element line 90, the proximalelement lines 90 may extend directly through openings in the proximalelements and/or through a layer or portion of a covering 100 on theproximal elements, or through a suture loop above or below a covering100.

FIGS. 17-18 illustrate the locking mechanism 106 showing the lockingmechanism 106 in the unlocked and locked positions respectively.Referring to FIG. 17, the locking mechanism 106 includes one or morewedging elements, such as rolling elements. In this embodiment, therolling elements comprise a pair of barbells 110 disposed on oppositesides of the stud 74, each barbell having a pair of generallycylindrical caps and a shaft therebetween. The barbells 110 and the stud74 are preferably comprised of cobalt chromium or stainless steel,however any suitable material may be used. The barbells 110 aremanipulated by hooked ends 112 of the release harness 108. When anupwards force is applied to the harness 108 by the lock line 92, thehooked ends 112 raise the barbells 110 against a spring 114, as shown inFIG. 17. This draws the barbells 110 up along a sidewall or slopingsurface 116 which unwedges the barbells 110 from against the stud 74. Inthis position, the stud 74 is free to move. Thus, when the lock line 92raises or lifts the harness 108, the locking mechanism 106 is in anunlocked position wherein the stud 74 is free to move the actuationmechanism 58 and therefore the distal elements 18 to any desiredposition. Release of the harness 108 by the lock line 92 transitions thelocking mechanism 106 to a locked position, illustrated in FIG. 18. Byreleasing the upwards force on the barbells 110 by the hooked ends 112,the spring 114 forces the barbells 110 downwards and wedges the barbells110 between the sloping surface 116 and the stud 74. This restrictsmotion of the stud 74, which in turn locks the actuation mechanism 58and therefore distal elements 18 in place. In addition, the stud 74 mayinclude one or more grooves 82 or indentations which receive thebarbells 110. This may provide more rapid and positive locking bycausing the barbells 110 to settle in a definite position, increase thestability of the locking feature by further preventing movement of thebarbells 110, as well as tangible indication to the user that thebarbell has reached a locking position. In addition, the grooves 82 maybe used to indicate the relative position of the distal elements 18,particularly the distance between the distal elements 18. For example,each groove 82 may be positioned to correspond with a 0.5 or 1.0 mmdecrease in distance between the distal elements 18. As the stud 74 ismoved, the barbells 110 will contact the grooves 82; by counting thenumber of grooves 82 that are felt as the stud 74 is moved, the user candetermine the distance between the distal elements 18 and can providethe desired degree of coaptation based upon leaflet thickness, geometry,spacing, blood flow dynamics and other factors. Thus, the grooves 82 mayprovide tactile feedback to the user.

The locking mechanism 106 allows the fixation device 14 to remain in anunlocked position when attached to the interventional tool 10 duringgrasping and repositioning and then maintain a locked position when leftbehind as an implant. It may be appreciated, however, that the lockingmechanism 106 may be repeatedly locked and unlocked throughout theplacement of the fixation device 14 if desired. Once the final placementis determined, the lock line 92 and proximal element lines 90 areremoved and the fixation device is left behind.

Additional locking mechanisms which may be used are disclosed in U.S.Pat. Nos. 7,563,267 (Attorney Docket No. 020489-001400US) and 7,226,467(Attorney Docket No. 020489-001700US), the entire contents of each isincorporated herein by reference.

D. Additional Embodiments of Fixation Devices

In other embodiments, the proximal elements may be manipulated toenhance gripping. For example, the proximal elements may be lowered tograsp leaflets or tissue between the proximal and distal elements, andthen the proximal elements may be moved to drag the leaflets or tissueinto the fixation device. In another example, the proximal elements maybe independently lowered to grasp the leaflets or tissue. This may beuseful for sequential grasping. In sequential grasping, one proximalelement is lowered to capture a leaflet or tissue portion between theproximal and distal elements. The fixation device is then moved,adjusted or maneuvered to a position for grasping another leaflet ortissue portion between another set of proximal and distal elements. Inthis position, the second proximal element is then lowered to grasp thisother leaflet or tissue portion.

Other exemplary embodiments of fixation devices are disclosed in U.S.Pat. Nos. 7,563,267 (Attorney Docket No. 020489-001400US) and 7,226,467(Attorney Docket No. 020489-001700US), the entire contents of each,fully incorporated herein by reference. One of skill in the art willappreciate that the various features of the disclosed fixation devicesmay be substituted with one another or used in combination with otherdisclosed features.

IV. Delivery Device

A. Overview of Delivery Device

FIG. 19 provides a perspective view of an embodiment of a deliverydevice or delivery catheter 300 which may be used to introduce andposition a fixation device as described above. The delivery catheter 300includes a shaft 302, having a proximal end 322 and a distal end 324,and a handle 304 attached to the proximal end 322. A fixation device(not shown) is removably coupleable to the distal end 324 for deliveryto a site within the body, typically for endovascular delivery to themitral valve. Thus, extending from the distal end 324 is a couplingstructure 320 for coupling with a fixation device. Also extending fromthe distal end 324 is an actuator rod 64. The actuator rod 64 isconnectable with the fixation device and acts to manipulate the fixationdevice, typically opening and closing the distal elements. Such couplingto a fixation device is illustrated in FIG. 20.

FIG. 20 illustrates an embodiment of a fixation device 14 coupled to thedistal end 324 of the delivery catheter 300. The shaft 302 is shownhaving a nose 318 near its distal end 324. In this embodiment, the nose318 has a flanged shape. Such a flanged shape prevents the nose 318 frombeing retracted into a guiding catheter or introducer as will bediscussed in later sections. However, it may be appreciated that thenose 318 may have any shape including bullet, rounded, blunt or pointed,to name a few. Extending from the nose 318 is a compression coil 326through which the coupling structure 320 and actuator rod 64 pass. Theactuator rod 64 is coupleable, as shown, with the stud 74 of thefixation device 14. Such coupling is illustrated in FIG. 21.

FIG. 21 illustrates a portion of the shaft 302 of the delivery catheter300 and a fixation device 14 which is coupleable with the catheter 300.Passing through the shaft 302 is the actuator rod 64. In thisembodiment, the actuator rod 64 comprises a proximal extremity 303 and adistal extremity 328, the distal extremity 328 of which is surrounded bya coil 330. The proximal extremity 303 is typically comprised ofstainless steel, nitinol, or Elgiloy®, to name a few, and may have adiameter in the range of 0.010 in. to 0.040 in., preferably 0.020 in. to0.030 in., more preferably 0.025 in., and a length in the range of 48 to72 in. The distal extremity 328 may be tapered, is typically comprisedof stainless steel, nitinol, or Elgiloy®, to name a few, and may have adiameter in the range of 0.011 to 0.025 in and a length in the range of4 to 12 in. Such narrowing increases flexibility of the distal end 324of the actuator rod 64. The actuator rod 64 further comprises a joiner332 which is attached to the distal extremity 328. The joiner 332 isremovably attachable with stud 74 of the fixation device 14. In thisembodiment, the joiner 332 has internal threads which mate with externalthreads on the stud 74 of the fixation device 14. As describedpreviously, the stud 74 is connected with the distal elements 18 so thatadvancement and retraction of the stud 74, by means of the actuator rod64, manipulates the distal elements. Likewise, the coupling member 19 ofthe fixation device 14 mates with the coupling structure 320 of thecatheter 300. Thus, the coupling member 19 and coupling structure 320function as previously described in relation to FIGS. 6A-6B.

Referring back to FIG. 20, the fixation device 14 may also include alocking mechanism which includes a release harness 108, as previouslydescribed in relation to FIGS. 16-18. Lock lines 92 are connected withthe release harness 108 to lock and unlock the locking mechanism 106 aspreviously described. The lock lines 92 extend through the shaft 302 ofthe delivery catheter 300 and may connect with the release harness 108in various arrangements as will be illustrated in later sections.Similarly, proximal element lines 90 extend through the shaft 302 of thedelivery catheter 300 and connect with the proximal elements 16. Theproximal elements 16 are raised and lowered by manipulation of theproximal element lines 90 as previously described. The proximal elementlines 90 may connect with the proximal elements 16 in variousarrangements as will be illustrated in later sections.

Referring back to FIG. 19, the handle 304 attached to the proximal end322 of the shaft 302 is used to manipulate the coupled fixation device14 and to optionally decouple the fixation device 14 for permanentimplantation. As described, the fixation device 14 is primarilymanipulated by the actuator rod 64, proximal element lines 90 and locklines 92. The actuator rod 64 manipulates the distal elements 18, theproximal element lines 90 manipulate the proximal elements 16 and thelock lines 92 manipulate the locking mechanism. In this embodiment, theactuator rod 64 may be translated (extended or retracted) to manipulatethe distal elements 18. This is achieved with the use of the actuatorrod control 314 which will be described in later sections. The actuatorrod 64 may also be rotated to engage or disengage the threaded joinerwith the threaded stud 74. This is achieved with the use of the actuatorrod handle 316 which will also be described in later sections. Further,the proximal element lines 90 may be extended, retracted, loaded withvarious amounts of tension or removed with the use of the proximalelement line handle 312. And, the lock lines 92 may be may be extended,retracted, loaded with various amounts of tension or removed with theuse of the lock line handle 310. Both of these handles 310, 312 will bedescribed in more detail in later sections. The actuator rod handle 316,actuator rod control 314, proximal element line handle 312 and lock linehandle 310 are all joined with a main body 308 within which the actuatorrod 64, proximal element lines 90 and lock lines 92 are guided into theshaft 302. The handle 304 further includes a support base 306 connectedwith the main body 308. The main body 308 is slideable along the supportbase 306 to provide translation of the shaft 302. Further, the main body308 is rotateable around the support base 306 to rotate the shaft.

While the embodiment of FIG. 21 is promising, in certain situations, theactuator rod 64 may deform and take a permanent set, especially alongthe thinner distal extremity region 328, during delivery of fixationdevice 14, thereby making it more challenging to properly deliver andattach the fixation device to the valve leaflets. For example, whensteering the distal portion of the delivery device through tight angles,(e.g. 90° or more), the distal tapered extremity 328 of the actuator rod64 may take a permanent set and thus may fail to return to asubstantially straight configuration after being deflected. FIGS.22A-22B illustrate an alternative embodiment of the actuator rodillustrated in FIG. 21. In this embodiment, the distal tapered extremity328 has been replaced with a flexible cable. Actuator rod 64 a is a longshaft or mandrel that generally takes the same form as actuator rod 64in FIG. 21. A flexible cable 2702 is disposed between a distal end ofthe actuator rod 64 a, and a proximal end of coupler or joiner 2708. Theflexible cable 2702 is disposed in a lumen of the delivery catheter(best seen in FIG. 32) and allows torque, tension, and compression to betransmitted to the coupler 2708, while allowing bending and flexingwithout resulting in the flexible cable taking a set. The walls of thecatheter lumen provide lateral support to the flexible cable 2702,thereby allowing it to transmit the torque and compression to thecoupler 2708. Actuation of the flexible cable 2702 would result inlateral bowing outward of the cable without the lateral support providedby the lumen walls. In this exemplary embodiment, a distal portion ofactuator rod 64 a is joined to a proximal end of the flexible cable 2702with a sleeve 2704. The sleeve 2704 has a central bore 2718 extendingtherethrough for receiving the flexible cable and the actuator rod. Thesleeve 2704 may then be crimped, swaged, or otherwise reduced indiameter in order to fixedly attach the two ends together. Inalternative embodiments, adhesives, welds, soldering joints, fasteners,etc. may also be used to join the two ends together. Similarly, aproximal end of the coupler 2708 may include a central bore 2718 that issized to receive a distal portion of the flexible cable 2702. In thisexemplary embodiment, the coupler is cylindrically shaped with aproximal portion 2716 having a larger diameter than the distal portion2710. After the proximal portion 2716 has been crimped or swaged ontothe flexible cable, the diameters of the proximal and distal portions ofthe coupler are preferably the same or substantially similar asillustrated in FIG. 22B. However, this is not intended to be limiting,and one of skill in the art will appreciate that the diameters of theproximal and distal portions of the coupler may also be different fromone another. The distal portion of the coupler may include a threadedbore 2712 which may be threadably attached to the fixation device 14,such as previously described above in FIGS. 7 and 21. FIG. 22Billustrates the actuator rod 64 a after it has been coupled with theflexible cable and the coupler by swaging.

The flexible cable is preferably resiliently biased to return to asubstantially straight or linear configuration, even after being bent ordeflected by 90° or more (relative to the longitudinal axis of theflexible cable). In preferred embodiments, the flexible cable is 25 cmor shorter, preferably 10 cm to 20 cm long, and more preferably 15 to 20cm long. The flexible cable also has an outer diameter preferably 0.015″to 0.035″ and more preferably is 0.020″ to 0.030″ and nominally is0.025″ although one of skill in the art will appreciate that otherdimensions may also be used. The actuator rod 64 a generally takes thesame form as actuator rod 64 in FIG. 21. The actuator rod 64 a andflexible cable 2702 are configured to transmit at least 0.25 inch-ouncesto at least 0.74 inch-ounces of torque with a substantially 1:1 torquetransmission ratio from the proximal end of the actuator mandrel to thedistal end of the flexible cable. In other embodiments, at least half ofthe torque applied to the proximal end of the actuator mandrel will betransmitted to the distal end of the flexible cable. In otherembodiments, at least 75%, or 80%, or 85%, or 90%, or 95% of the torquewill be transmitted. This torque is required to threadably engage anddisengage the coupler 2708 from the fixation device. The fixation deviceis often disengaged from the coupler after the valve has beensatisfactorily repaired. Additionally, when disposed in a lumen of thedelivery catheter, the actuator rod 64 a and the flexible cable 2702 arealso designed to transmit at least 1 pound, and preferably at least 2.5pounds of compressive force distally to the fixation device in order toactuate the distal elements thereof. Also, the actuator rod and flexiblecable can withstand at least 5 pounds, and more preferably at least 14.7pounds of tensile force without substantial stretching or elongation.This force is experienced when actuating the fixation device to closethe distal elements. Various metals, polymers, and other materials maybe used for the actuator rod, flexible cable, sleeve, and coupler.However, in preferred embodiments, the coupler is fabricated from 17-4H1150 stainless steel, while the cable comprises 304V stainless steel,and the mandrel is 304 stainless steel with an ultraspring wire temper.While various preferred sizes and operating parameter of the actuatorrod and cable assembly are disclosed above, one of skill in the art willappreciate that these are not intended to be limiting. The size of thevarious components may be increased or decreased to accommodate variousapplications. Moreover, the operating characteristics (e.g. ability totransmit a certain torque, or tension, etc.) may similarly be adjustedin order to accommodate different applications.

Various configurations of the flexible cable may be used, such as thecable illustrated in FIGS. 23A-26B. The flexible cable of FIG. 23A-26Bis a stranded cable with a reverse wind designed to have a high torquetransmission ratio in the counterclockwise direction. The torquetransmission ratio in the clockwise direction is less than that of thecounterclockwise direction due to the direction the wires are wound.This cable includes four layers of wires. The innermost layer 2802 isseen in FIG. 23A and includes three wires 2802 a, 2802 b, 2802 chelically wound together. FIG. 23B illustrates a cross-section of cable2802 taken along the line A-A. The next layer 2902 comprises nineadditional strands of wire 2904 wrapped around the innermost layer 2802as illustrated in FIG. 24A. FIG. 24B is a cross-section taken along theline B-B. The next layer 3002 is illustrated in FIG. 25A, and comprisesten additional strands of wire 3006 wrapped around layer 2902, and across-section taken along line D-D is shown in FIG. 25B. Finally, theoutermost layer 3102 comprises ten more wires 3108 wrapped around layer3002 as seen in FIG. 26A, with cross-sectional taken along line D-D inFIG. 26B. One of skill in the art will appreciate the various strandmaterial characteristics (e.g. diameter, tensile strength, etc.) andwinding patterns that may be used.

An alternative embodiment is illustrated in FIGS. 27A-31B. Thisembodiment is similar to that previously described above, with the majordifference being that after the cable has been wound, it is drawnthereby altering the surface finish and some of the mechanicalcharacteristics. FIG. 27A illustrates the innermost layer 3202 whichincludes three wires 3204 wound together, as seen in the cross-sectionof FIG. 27B taken along the line A-A. FIG. 28A shows the next layer 3302which includes nine wires 3304 wrapped around the innermost layer 3202.FIG. 28B shows a cross-section taken along line B-B. The next layer 3402of wires are shown in FIG. 29A having ten wires 3404 wrapped around theprevious layer 3302, as illustrated in the cross-section of FIG. 29Btaken along line C-C. The outermost layer 3502 is shown in FIG. 30A andincludes another ten wires 3504 wrapped around the previous layer 3402,with cross-section taken along line D-D in FIG. 30B. The assembly offour layers of wire are then drawn in order to alter the surface finishof the cable and to alter material properties of the finished cableassembly to a desired value. FIG. 31A illustrates the finished cableassembly 3602 with cross-section taken along line E-E in FIG. 31B. Oneof skill in the art will appreciate that other cable configurations maybe used, and that these are only exemplary embodiments.

B. Delivery Catheter Shaft

FIG. 32 illustrates a cross-sectional view of the delivery cathetershaft 302 of FIG. 19. In this embodiment, the shaft 302 has a tubularshape with inner lumen 348 and is comprised of a material which provideshoop strength while maintaining flexibility and kink resistance, such asa braided laminated material. Such material may include stainless steelbraided or coiled wire embedded in a polymer such as polyurethane,polyester, Pebax, Grilamid TR55, and AESNO to name a few. To providefurther support and hoop strength, a support coil 346 is disposed withinthe lumen 348 of shaft 302 as illustrated in FIG. 32.

Passing through the support coil 346 are a variety of elongated bodies,including tubular guides and cylindrical rods. For example, one type oftubular guide is a compression coil 326 extending through lumen 348 fromthe proximal end 322 to the distal end 324 of the shaft 302, and theactuator rod 64 extends through the compression coil 326. Therefore, thecompression coil typically has a length in the range of 48 to 60 in. andan inner diameter in the range of 0.020 to 0.035 in. to allow passage ofthe actuator rod 64 therethrough. The actuator rod 64 is manipulatableto rotate and translate within and relative to the compression coil 326.The compression coil 326 allows lateral flexibility of the actuator rod64 and therefore the shaft 302 while resisting buckling and providingcolumn strength under compression. The compression coil may be comprisedof 304V stainless steel to provide these properties.

To provide additional tensile strength for the shaft 302 and to minimizeelongation, a tension cable 344 may also pass through the support coil346. The tension cable 344 extends through lumen 348 from the proximalend 322 to the distal end 324 of the shaft 302. Therefore, the tensioncable 344 typically has a diameter in the range of 0.005 in. to 0.010in. and a length in the range of 48 to 60 in. In preferred embodiments,the tension cable 344 is comprised of 304V stainless steel.

In addition, at least one lock line shaft 341 having a tubular shape maybe present having a lock line lumen 340 through which lock lines 92 passbetween the lock line handle 310 and the locking mechanism 106. The lockline shaft 341 extends through lumen 348 from the proximal end 322 tothe distal end 324 of the shaft 302. Therefore, the lock line shaft 341typically has a length in the range of 48 to 60 in., an inner diameterin the range of 0.016 to 0.030 in., and an outer diameter in the rangeof 0.018 to 0.034 in. In preferred embodiments, the lock line shaft 341is comprised of a 304V stainless steel coil however other structures ormaterials may be used which provide kink resistance and compressionstrength.

Similarly, at least one proximal element line shaft 343 having a tubularshape may be present having a proximal element line lumen 342. Proximalelement lines 90 pass through this lumen 342 between the proximalelement line handle 312 and the proximal elements 16. Thus, the proximalelement line shaft 343 extends through lumen 348 from the proximal end322 to the distal end 324 of the shaft 302. Therefore, the proximalelement line shaft 343 typically has a length in the range of 48 to 60in., an inner diameter in the range of 0.016 to 0.030 in., and an outerdiameter in the range of 0.018 to 0.034 in. In preferred embodiments,the proximal element line shaft 343 is comprised of a 304V stainlesssteel coil however other structures or materials may be used whichprovide kink resistance and compression strength.

In this embodiment, the elongated bodies (compression coil 326 enclosedactuator rod 64, tension cable 344, lock line shaft 342, proximalelement line shaft 343) each “float” freely in inner lumen 348 withinthe support coil 346 and are fixed only at the proximal end 322 anddistal end 324 of shaft 302. The lumen 348 is typically filled andflushed with heparinized saline during use. Alternatively or inaddition, the lumen 348 may be filled with one or more fillers, such asflexible rods, beads, extruded sections, gels or other fluids.Preferably the fillers allow for some lateral movement or deflection ofthe elongated bodies within lumen 348 but in some cases may restrictsuch movement. Typically, the elongated bodies are fixed at the proximaland distal ends of the shaft and are free to move laterally androtationally therebetween. Such freedom of movement of the elongatedbodies provides the shaft 302 with an increased flexibility as theelongated bodies self-adjust and reposition during bending and/ortorqueing of the shaft 302. It may be appreciated that the elongatedbodies may not be fixed at the proximal and distal ends. The elongatedbodies are simply unconstrained relative to the shaft 302 in at leastone location so as to be laterally moveable within the lumen 348.Preferably the elongated bodies are unrestrained in at least a distalportion of the catheter, e.g. 5-15 cm from the distal end 324, so as toprovide maximum flexibility in the distal portion.

It may be appreciated, however, that alternate shaft 302 designs mayalso be used. For example, referring to FIG. 33, in this embodiment theshaft 302 again has a tubular shape with an inner lumen 348 and asupport coil 346 disposed within the lumen 348 of shaft 302. Filling theinner lumen 348 within the support coil 346 is an extrusion 334 havinglumens through which pass a variety of elongated bodies, including thecompression coil 326 enclosed actuator rod 64, tension cable 344, lockline shafts 342, and proximal element line shafts 343, as shown. Thesupport coil 346 and elongated bodies may have the same geometries andbe comprised of the same materials as described above in relation toFIG. 32.

Alternatively, as shown in FIG. 34, the shaft 302 may include aninternal partition 350 to create multiple lumens within the shaft 302.For example, the partition 350 may have a central lumen 352 for passageof the actuator rod 64, optionally surrounded by the compression coil326. In addition, the partition 350 may also create at least one lockline lumen 340 for passage of a lock line 92 and at least one proximalelement line lumen 341 for passage of a proximal element line 90.Optionally, each of the lumens defined by partition 350 may be linedwith a kink-resistant element, such as a coil as in previousembodiments.

FIGS. 34A-34B illustrate embodiments of the nose 318 of the shaft 302.In FIG. 34A, the nose 318 comprises a tip ring 280 and a lock ring 282.In preferred embodiments, Epoxy and PEBAX are deposited between the tipring 280 and the lock ring 282 to bond them together. The lock ring 282has a geometry to mate with the tip ring 280 to maintain relativealignment between the two. FIG. 34B illustrates another embodiment ofthe nose 318 of the shaft 302. Here, the tip ring 280 is covered by asoft tip 284 to provide a more atraumatic tip and a smoother transitionto the shaft.

C. Lock Line Arrangements

As mentioned previously, when lock lines 92 are present, the lines 92pass through at least one lock line lumen 340 between the lock linehandle 310 and the locking mechanism 106. The lock lines 92 engage therelease harnesses 108 of the locking mechanism 106 to lock and unlockthe locking mechanism 106 as previously described. The lock lines 92 mayengage the release harnesses 108 in various arrangements, examples ofwhich are illustrated in FIG. 35A. In this exemplary embodiment, twolock line lumens 340 are present within the shaft 302 of the deliverycatheter 300 terminating at the nose 318. The lumens 340 are disposed onalternate sides of the actuator rod 64 so that each lumen 340 isdirected toward a release harness 108.

FIG. 35A illustrates an embodiment wherein two lock lines 92, 92′ passthrough a single lock line lumen 340 and are threaded through a releaseharness 108 on one side of the actuator rod 64 (the actuator rod 64 isshown without surrounding housing such as coupling structure, forclarity). The lock lines 92, 92′ are then separated so that each lockline passes on an opposite side of the actuator rod 64. The lock lines92, 92′ then pass through the release harness 108′ on the opposite sideof the actuator rod 64 and continue together passing through a anothersingle lock line lumen 340′. This lock line arrangement is the samearrangement illustrated in FIG. 20.

It may be appreciated that a variety of lock line arrangements may beused and are not limited to the arrangements illustrated and describedabove. The various arrangements allow the harnesses 108 to bemanipulated independently or jointly, allow various amounts of tensionto be applied and vary the force required for removal of the lock lineswhen the fixation device is to be left behind. For example, a singlelock line passing through one or two lumens may be connected to bothrelease harnesses for simultaneous application of tension.

D. Proximal Element Line Arrangements

As mentioned previously, when proximal element lines 90 are present, thelines 90 pass through at least one proximal element line lumen 342between the proximal element line handle 312 and at least one proximalelement 16. The proximal element lines 90 engage the proximal elements16 to raise or lower the element 16 as previously described. Theproximal element lines 90 may engage the proximal elements 16 in variousarrangements, examples of which are illustrated in FIG. 36A. In eachembodiment, two proximal element line lumens 342 are present within theshaft 302 of the delivery catheter 300 terminating at the nose 318. Thelumens 342 are disposed on alternate sides of the actuator rod 64 (theactuator rod 64 is shown without surrounding housing such as couplingstructure, for clarity) so that each lumen 342 is directed toward aproximal element 16.

FIG. 36A illustrates an embodiment wherein one proximal element line 90passes through a single proximal element line lumen 342. The proximalelement line 90 is threaded through an eyelet 360 of a proximal element16 on one side of the actuator rod 64, passes over the actuator rod 64and is threaded through an eyelet 360′ of another proximal element 16′on the other side of the actuator rod 64. The proximal element line 90then passes through another single proximal element line lumen 342′.This proximal element line arrangement is the same arrangementillustrated in FIG. 20.

It may be appreciated that a variety of proximal element linearrangements may be used and are not limited to the arrangementsillustrated and described above. The various arrangements allow theproximal elements to be manipulated independently or jointly, allowvarious amounts of tension to be applied and vary the force required forremoval of the proximal element lines when the fixation device is to beleft behind. For example, a single proximal element line passing throughone or two lumens in shaft 302 may be used for simultaneous actuation ofboth proximal elements.

E. Main Body of Handle

FIG. 37 illustrates an embodiment of the handle 304 of the deliverycatheter 300. As mentioned previously, the actuator rod handle 316,actuator rod control 314, proximal element line handle 312 and lock linehandle 310 are all joined with the main body 318. The handle 304 furtherincludes a support base 306 connected with the main body 308. The mainbody 308 is slideable along the support base 306 to provide translationof the shaft 302 and the main body 308 is rotateable around the supportbase 306 to rotate the shaft.

FIG. 38 provides a partial cross-sectional view of the main body 308 ofthe handle 304 depicted in FIG. 37. As shown, the main body 308 includesa sealed chamber 370 within which the actuator rod 64, proximal elementlines 90 and lock lines 92 are guided into the shaft 302. The sealedchamber 370 is in fluid communication with the inner lumen 348 of shaft302 and is typically filled with saline and flushed with heparin orheparinized saline. The sealed chamber 370 has a seal 372 along itsperimeter to prevent leakage and the introduction of air to the chamber370. Any air in the chamber 370 may be bled from the chamber 370 by oneor more luers 374 which pass through the main body 308 into the chamber370 as illustrated in FIG. 37. In this embodiment, the handle 304includes two such luers 374, one on each side of the main body 308(second luer symmetrically positioned on backside of main body 308 inFIG. 37, hidden from view). Referring now to FIG. 38, the sealed chamber370 also has various additional seals, such as an actuator rod seal 376which surrounds the actuator rod 64 where the actuator rod 64 enters thesealed chamber 370, and a shaft seal 378 which surrounds the shaft 302where the shaft 302 enters the sealed chamber 370.

F. Lock Line Handle and Proximal Element Line Handle

As mentioned previously, the lock lines 92 may be may be extended,retracted, loaded with various amounts of tension or removed using thelock line handle 310. Likewise, the proximal element lines 90 may beextended, retracted, loaded with various amounts of tension or removedusing the proximal element line handle 312. Both of these handles 310,312 may be similarly designed to manipulate the appropriate lines 90, 92passing therethrough.

FIG. 39 illustrates an embodiment of a lock line handle 310 having locklines 92 passing therethrough. The lock line handle 310 has a distal end384, a proximal end 382 and an elongate shaft 383 therebetween. Thedistal end 382 is positionable within the sealed chamber 370 so that theproximal end 382 extends out of the chamber 370, beyond the main body308. The free ends of the lock lines 92 are disposed near the proximalend 382, passing through the wall of the handle 310 near a threaded nub390. The handle 310 further includes a cap 388 which is positionable onthe nub 309. Internal threading with the cap 388 mates with thethreading on the threaded nub 390 so that the cap 388 holds the freeends of the lock lines 92 between the cap 388 and the nub 390 and/orother portions of the handle 310 by friction. The lock lines 92 passthrough a central lumen (not shown) of the elongate shaft 383, extendthrough the sealed chamber 370 (as shown in FIG. 38) and extend throughthe shaft 302 to the locking mechanism 106.

Disposed near the distal end 384 of the handle 310 is at least one wing392. In the embodiment of FIG. 39, two wings 392 are present, each wing392 disposed on opposite sides of the elongate shaft 383. The wings 392extend radially outwardly and curve proximally so that a portion isparallel to the elongate shaft 383, as shown. It may be appreciated thatthe wings 392 may alternatively have the shape of solid or continuousprotrusions which extend radially and have a portion which is parallelto the elongate shaft 383. The wings 392 are used to hold the lock linehandle 310 in a desired position which in turn holds the lock under adesired load of tension, as will be described further below. The handle310 also includes a finger grip 386 near the proximal end 382 whichextends radially outwardly in alignment with the radial extension of theat least one wing 392. Thus, the user may determine the orientation ofthe wings 392 within the sealed chamber 370 from the orientation of thefinger grip 386 outside of the main body 308. The finger grip 386 mayalso serve an ergonomic purpose to assist in manipulating the handle310.

The portion of the wings 392 parallel to the elongate shaft 383 havegrooves or serrations 394. The serrations 394 are used to apply tensionto the lock lines 92. As shown in FIG. 39A, the lock line handle 310 ispositioned within a semi-tube 400 which is disposed within the sealedchamber 370. The semi-tube 400 comprises a top half 402 and a bottomhalf 404, each half 402, 404 having grooves or serrations 406 which matewith the serrations 394 of the wings 392. Thus, when the wings 392 arerotated to mate the serrations 394, 406, as shown in FIG. 40A, theelongate shaft 383 is held in place. Likewise, the wings 392 may berotated, as shown in FIG. 40B, so that the wings 392 are disposedbetween the halves 402, 404 and the serrations 394, 406 are disengaged.In this position, the shaft 383 may be translated to apply or releasetension in the lock lines 92. Thus, tension in the lines 92 may beadjusted by rotating the shaft 383 to disengage the serrations 394, 406,translating the shaft 383 and then rotating the shaft 383 back toreengage the serrations 394, 406. Alternatively, the finger grip 386 maybe pulled to apply tension to the lock lines 92. Pulling the finger grip386 translates the lock line handle 310 within the semi-tube 400. Suchtranslation is achievable due to angling of the serrations 394, 406 andflexibility of wings 382. However, the angling of the serrations 394,406 prevents translation in the opposite direction, i.e. by pushing thefinger grip 386. Therefore, to release tension from the lock lines 92,the shaft 383 is rotated to disengage the serrations 394, 406, allowingtranslation of the shaft 383, and then the shaft 383 is rotated back toreengage the serrations 394, 406.

To remove the lock lines 92, the cap 388 is removed from the threadednub 390 exposing the free ends of the lock lines 92. If one lock line 92is present having two free ends, continuous pulling on one of the freeends draws the entire length of lock line 92 out of the catheter 300. Ifmore than one lock line 92 is present, each lock line 92 will have twofree ends. Continuous pulling on one of the free ends of each lock line92 draws the entire length of each lock line 92 out of the catheter 300.

It may be appreciated that the proximal element line handle 312 hascorresponding features to the lock line handle 310 and operates in thesame manner as illustrated in FIGS. 39A, 40A-40B. It may also beappreciated that other mechanisms may be used for manipulating the locklines 92 and proximal element lines 90, such as including buttons,springs, levers and knobs.

G. Actuator Rod Control and Handle

The actuator rod 64 may be manipulated using the actuator rod control314 and the actuator rod handle 316. FIG. 41 provides a cross-sectionalview of a portion of the handle 304 which includes the actuator rodcontrol 314 and the actuator rod handle 316. The actuator rod handle 316is located at the proximal end of the handle 314. The actuator rodhandle 316 is fixedly attached to the proximal end of the actuator rod64. The actuator rod 64 is inserted through a collet 426 which isdisposed within a holder 428 as shown. The holder 428 has externalthreads 434 which mate with internal threads 432 of the actuator rodcontrol 314. Thus, rotation of the actuator rod control 314 causes theholder 428 to translate along the actuator rod control 314 by action ofthe threading, as will be described in more detail below. The actuatorrod control 314 is rotatably coupled with the main body 308 of thehandle 304 and is held in place by a lip 430.

Referring to FIG. 41A, the actuator rod control 314 may be manuallyrotated in a clockwise or counter clockwise direction, as indicated byarrow 436. Rotation of the actuator rod control 314 translates (extendsor retracts) the actuator rod 64 to manipulate the distal elements 18 ofthe fixation device 14. Specifically, rotation of the actuator rodcontrol 314 causes the external threads 434 of the adjacent holder 428to translate along the mated internal threads 432 of the actuator rodcontrol 314. Rotation of the holder 428 itself is prevented by holdingpins 424 which protrude from the holder 428 and nest into grooves 438 inthe main body 308 of the handle 304. As the holder 428 translates, eachholding pin 424 translates along its corresponding groove 438. Since thecollet 426 is attached to the holder 428, the collet 426 translatesalong with the holder 428. To simultaneously translate the actuator rod64, the actuator rod 64 is removably attached to the collet 426 by a pin422. The pin 422 may have any suitable form, including a clip-shapewhich partially wraps around the collet 426 as illustrated in FIG. 41.Thus, rotation of the actuator rod control 314 provides fine control oftranslation of the actuator rod 64 and therefore fine control ofpositioning the distal elements 18.

Referring to FIG. 41B, removal of the pin 422, as shown, allowsdisengagement of the actuator rod handle 316 and fixedly attachedactuator rod 64 from the collet 426. Once disengaged, the actuator rod64 may be rotated, as indicated by arrow 440, by manually rotating theactuator rod handle 316. As described previously, rotation of theactuator rod 64 engages or disengages the threaded joiner 332 of thedelivery catheter 300 from the threaded stud 74 of the fixation device14. This is used to attach or detach the fixation device 14 from thedelivery catheter 300. In addition, when the actuator rod 64 is in thedisengaged state, the actuator rod 64 may optionally be retracted andoptionally removed from the catheter 300 by pulling the actuator rodhandle 316 and withdrawing the actuator rod 64 from the handle 304.

Depending on the application, the location of the target site, and theapproach selected, the devices of the invention may be modified in wayswell known to those of skill in the art or used in conjunction withother devices that are known in the art. For example, the deliverycatheter may be modified in length, stiffness, shape and steerabilityfor a desired application. Likewise, the orientation of the fixationdevice relative to the delivery catheter may be reversed or otherwisechanged. The actuation mechanisms may be changed to be driven inalternate directions (push to open, pull to close, or pull to open, pushto close). Materials and designs may be changed to be, for example, moreflexible or more rigid. And the fixation device components may bealtered to those of different size or shape. Further, the deliverycatheter of the present invention may be used to deliver other types ofdevices, particularly endovascular and minimally invasive surgicaldevices used in angioplasty, atherectomy, stent-delivery, embolicfiltration and removal, septal defect repair, tissue approximation andrepair, vascular clamping and ligation, suturing, aneurysm repair,vascular occlusion, and electrophysiological mapping and ablation, toname a few. Thus, the delivery catheter of the present invention may beused for applications in which a highly flexible, kink-resistant deviceis desirable with high compressive, tensile and torsional strength.

V. Multi-Catheter Guiding System

A. Overview of Guiding System

Referring to FIG. 42, an embodiment of a multi-catheter guiding system 1of the present invention is illustrated. The system 1 comprises an outerguide catheter 1000, having a proximal end 1014, a distal end 1016, anda central lumen 1018 therethrough, and an inner guide catheter 1020,having a proximal end 1024, distal end 1026 and central lumen 1028therethrough, wherein the inner guide catheter 1020 is positionedcoaxially within the central lumen 1018 of the outer guide catheter1000, as shown. The distal ends 1016, 1026 of catheters 1000, 1020,respectively, are sized to be passable to a body cavity, typicallythrough a body lumen such as a vascular lumen. Thus, the distal end 1016preferably has an outer diameter in the range of approximately 0.040 in.to 0.500 in., more preferably in the range of 0.130 in. to 0.320 in. Thecentral lumen 1018 is sized for the passage of the inner guide catheter1020; the distal end 1026 preferably has an outer diameter in the rangeof approximately 0.035 in. to 0.280 in., more preferably 0.120 in to0.200 in. The central lumen 1028 is sized for the passage of a varietyof devices therethrough. Therefore, the central lumen 1028 preferablyhas an inner diameter in the range of approximately 0.026 in. to 0.450in., more preferably in the range of 0.100 in. to 0.180 in.

FIG. 42 illustrates an interventional catheter 1030 positioned withinthe inner guide catheter 1020 which may optionally be included in system1, however other interventional devices may be used. The interventionalcatheter 1030 has a proximal end 1034 and a distal end 1036, wherein aninterventional tool 1040 is positioned at the distal end 1036. In thisembodiment, the interventional tool 1040 comprises a detachable fixationdevice or clip. Optionally, the interventional catheter 1030 may alsoinclude a nosepiece 1042 having a stop 1043, as shown. The stop 1043prevents the interventional tool 1040 from entering the central lumen1028 of the inner guide catheter 1020. Thus, the interventional catheter1030 may be advanced and retracted until the stop 1043 contacts thedistal end 1026 of the inner guiding catheter 1020 preventing furtherretraction. This may provide certain advantages during some procedures.It may be appreciated that in embodiments which include such a stop1043, the interventional catheter 1030 would be pre-loaded within theinner guide catheter 1020 for advancement through the outer guidingcatheter 1000 or both the interventional catheter 1030 and the innerguiding catheter 1020 would be pre-loaded into the outer guidingcatheter 1000 for advancement to the target tissue. This is because thestop 1043 prevents advancement of the interventional catheter 1030through the inner guiding catheter 1020.

The outer guide catheter 1000 and/or the inner guide catheter 1020 areprecurved and/or have steering mechanisms, embodiments of which will bedescribed later in detail, to position the distal ends 1016, 1026 indesired directions. Precurvature or steering of the outer guide catheter1000 directs the distal end 1016 in a first direction to create aprimary curve while precurvature and/or steering of the inner guidecatheter 1020 directs distal end 1026 in a second direction, differingfrom the first, to create a secondary curve. Together, the primary andsecondary curves form a compound curve. Advancement of theinterventional catheter 1030 through the coaxial guide catheters 1000,1020 guides the interventional catheter 1030 through the compound curvetoward a desired direction, usually in a direction which will allow theinterventional catheter 1030 to reach its target.

Steering of the outer guide catheter 1000 and inner guide catheter 1020may be achieved by actuation of one or more steering mechanisms.Actuation of the steering mechanisms is achieved with the use ofactuators which are typically located on handles connected with each ofthe catheters 1000, 1020. As illustrated in FIG. 42, handle 1056 isconnected to the proximal end 1014 of the outer guide catheter 1000 andremains outside of the patient's body during use. Handle 1056 includessteering actuator 1050 which may be used to bend, arc or reshape theouter guide catheter 1000, such as to form a primary curve. Handle 1057is connected to the proximal end (not shown) of the inner guide catheter1020 and may optionally join with handle 1056 to form one larger handle,as shown. Handle 1057 includes steering actuator 1052 which may be usedto bend, arc or reshape the inner guide catheter 1020, such as to form asecondary curve and move the distal end 1026 of the inner guide catheter1020 through an angle theta, as will be described in a later section.

In addition, locking actuators 1058, 1060 may be used to actuate lockingmechanisms to lock the catheters 1000, 1020 in a particular position.Actuators 1050, 1052, 1058, 1060 are illustrated as buttons, however itmay be appreciated that these and any additional actuators located onthe handles 1056, 1057 may have any suitable form including knobs,thumbwheels, levers, switches, toggles, sensors or other devices. Otherembodiments of the handles will be described in detail in a latersection.

In addition, the handle 1056 may include a numerical or graphicaldisplay 1061 of information such as data indicating the position thecatheters 1000, 1020, or force on actuators. It may also be appreciatedthat actuators 1050, 1052, 1058, 1060 and any other buttons or screensmay be disposed on a single handle which connects with both thecatheters 1000, 1020.

B. Example Positions

FIGS. 43A-43D illustrate examples of positions that the catheters 1000,1020 may hold. Referring to FIG. 43A, the outer guide catheter 1000 maybe precurved and/or steered into a position which includes a primarycurve 1100. The primary curve 1100 typically has a radius of curvature1102 in the range of approximately 0.125 in. to 1.000 in., preferably inthe range of approximately 0.250 in. to 0.500 in. or forms a curve inthe range of approximately 0° to 120°. As shown, when the positionincludes only a primary curve 1100, the distal end 16 lies in a singleplane X. An axis x, transversing through the center of the central lumen18 at the distal end 16, lies within plane X.

Referring to FIG. 43B, the inner guide catheter 1020 extends through thecentral lumen 1018 of the outer guide catheter 1000. The inner guidecatheter 1020 may be precurved and/or steered into a position whichincludes a secondary curve 1104. The secondary curve 1104 typically hasa radius of curvature 10600 in the range of approximately 0.050 in. to0.750 in., preferably in the range of approximately 0.125 in. to 0.250in. or forms a curve in the range of approximately 0° to 180°. Thesecondary curve 1104 can lie in the same plane as the primary curve1100, plane X, or it can lie in a different plane, such as plane Z asshown. In this example, plane Z is substantially orthogonal to plane X.Axis z, transversing through the center of the central lumen 1028 of theinner guide catheter 1020 at the distal end 1026, lies within plane Z.In this example, axis x and axis z are at substantially 90 degree anglesto each other; however, it may be appreciated that axis x and axis z maybe at any angle in relation to each other. Also, although in thisexample the primary curve 1100 and the secondary curve 1104 lie indifferent planes, particularly in substantially orthogonal planes, thecurves 1100, 1104 may alternatively lie in the same plane.

Referring now to FIG. 43C, the inner guide catheter 1020 may be furthermanipulated to allow the distal end 1026 to move through an angle theta1070. The angle theta 1070 is in the range of approximately −180° to+180°, typically in the range of −90° to +90°, possibly in the range of−60° to +60°, −45° to +45°, −30° to +30° or less. As shown, the angletheta 1070 lies within a plane Y. In particular, axis y, which runsthrough the center of the central lumen 1028 at the distal end 1026,forms the angle theta 1070 with axis z. In this example, plane Y isorthogonal to both plane X and plane Z. Axes x, y, z all intercept at apoint within the central lumen 1028 which also coincides with theintersection of planes X, Y, Z.

Similarly, FIG. 43D illustrates movement of the distal end 1026 throughan angle theta 1070 on the opposite side of axis z. Again, the angletheta 1070 is measured from the axis z to the axis y, which runs throughthe center of the central lumen 1016 at the distal end 1026. As shown,the angle theta 1070 lies in plane Y. Thus, the primary curve 1100,secondary curve 1104, and angle theta 1070 can all lie in differentplanes, and optionally in orthogonal planes. However, it may beappreciated that the planes within which the primary curve 1100,secondary curve 1104 and angle theta 1070 lie may be mutually dependentand therefore would allow the possibility that some of these lie withinthe same plane.

In addition, the outer guide catheter 1000 may be pre-formed and/orsteerable to provide additional curves or shapes. For example, asillustrated in FIG. 44A, an additional curve 1110 may be formed by theouter guide catheter 1000 proximal to the primary curve 1100. In thisexample, the curve 1110 provides lift or raises the distal end 1016 ofthe outer guide catheter 1000, which in turn raises the distal end 1026of the inner guide catheter 1020. Such lifting is illustrated in FIG.449B. Here, the system 1 is shown prior to lifting in dashed linewherein the axis y′ passes through the intersection of axis z and axisx′. After application of curve 1110, the distal portion of the system 1is lifted in the direction of axis z so that axis x′ is raised to axisx″ and axis y′ is raised to axis y″. This raises distal end 1026 to adesired height.

The articulated position of the multi-catheter guiding system 1illustrated in FIGS. 43A-43D and FIGS. 44A-44B is particularly usefulfor accessing the mitral valve. FIGS. 45A-45D illustrate a method ofusing the system 1 for accessing the mitral valve MV. To gain access tothe mitral valve, the outer guide catheter 1000 may be tracked over adilator and guidewire from a puncture in the femoral vein, through theinferior vena cava and into the right atrium. As shown in FIG. 45A, theouter guide catheter 1000 may be punctured through a fossa F in theinteratrial septum S. The outer guide catheter 1000 is then advancedthrough the fossa F and curved by the primary curve 1100 so that thedistal end 1016 is directed over the mitral valve MV. Again, it may beappreciated that this approach serves merely as an example and otherapproaches may be used, such as through the jugular vein, femoralartery, port access or direct access, to name a few. Positioning of thedistal end 1016 over the mitral valve MV may be accomplished byprecurvature of the outer guide catheter 1000, wherein the catheter 1000assumes this position when the dilator and guidewire are retracted,and/or by steering of the outer guide catheter 1000 to the desiredposition. In this example, formation of the primary curve 1100 moves thedistal end 1016 within a primary plane, corresponding to previous planeX, substantially parallel to the valve surface. This moves the distalend 1016 laterally along the short axis of the mitral valve MV, andallows the distal end 1016 to be centered over the opening O between theleaflets LF.

Referring to FIG. 45B, the inner guide catheter 1020 is advanced throughthe central lumen 1018 of the outer guide catheter 1000 and the distalend 1026 is positioned so that the central lumen 1028 is directed towardthe target tissue, the mitral valve MV. In particular, the central lumen1028 is to be directed toward a specific area of the mitral valve MV,such as toward the opening O between the valve leaflets LF, so that aparticular interventional procedure may be performed. In FIG. 45B, theinner guide catheter 1020 is shown in a position which includes asecondary curve 1104 in a secondary plane, corresponding to previousplane Z. Formation of the secondary curve 1104 moves the distal end 1026vertically and angularly between the commissures C, directing thecentral lumen 1028 toward the mitral valve MV. In this position aninterventional device or catheter 1030 which is passed through thecentral lumen 1028 would be directed toward and/or through the openingO. Although the primary curve 1100 and the secondary curve 1104 may bevaried to accommodate different anatomical variations of the valve MVand different surgical procedures, further adjustment may be desiredbeyond these two curvatures for proper positioning of the system 1.

Referring to FIG. 45C, the distal end 1026 of the inner guide catheter1020 may be positioned through an angle theta 1070. This moves thedistal end 1026 vertically and angularly through a theta plane,corresponding to previous plane Y. Movement of the distal end 1026through the angle theta 1070 in either direction is shown in dashed linein FIG. 45C. Such movement can be achieved by precurvature and/or bysteering of the catheter 1020. Consequently, the central lumen 1028 canbe directed toward the mitral valve MV within a plane which differs fromthe secondary plane. After such movements, the inner guide catheter 1020will be in a position so that the opening of the central lumen 1028 atthe end 1016 faces the desired direction. In this case, the desireddirection is toward the center of and orthogonal to the mitral valve.

In some instances, it is desired to raise or lower the distal end 1026so that it is at a desired height in relation to the mitral valve MV.This may be accomplished by precurvature and/or by steering of the outerguide catheter 1000 to form additional curve 1110. Generally this isused to lift the distal end 1026 above the mitral MV wherein suchlifting was illustrated in FIG. 44B.

When the curvatures in the catheters 1000, 1020 are formed by steeringmechanisms, the steering mechanisms may be locked in place by a lockingfeature. Locking can provide additional stiffness and stability in theguiding system 1 for the passage of interventional devices or catheters1030 therethrough, as illustrated in FIG. 42. The interventionalcatheter 1030 can be passed through the central lumen 1028 toward thetarget tissue, in this case the mitral valve MV. Positioning of thedistal end 1026 over the opening O, as described above, allows thecatheter 1030 to pass through the opening O between the leaflets LF ifdesired, as shown in FIG. 45D. At this point, any desired procedure maybe applied to the mitral valve for correction of regurgitation or anyother disorder.

C. Steering Mechanisms

As described previously, the curvatures may be formed in the catheters1000, 1020 by precurving, steering or any suitable means. Precurvinginvolves setting a specific curvature in the catheter prior to usage,such as by heat setting a polymer or by utilizing a shape-memory alloy.Since the catheters are generally flexible, loading of the catheter on aguidewire, dilator obturator or other introductory device straightensthe catheter throughout the curved region. Once the catheter ispositioned in the anatomy, the introductory device is removed and thecatheter is allowed to relax back into the precurved setting.

To provide a higher degree of control and variety of possiblecurvatures, steering mechanisms may be used to create the curvatures andposition the catheters. In some embodiments, the steering mechanismscomprise cables or pullwires within the wall of the catheter. As shownin FIG. 46A, the outer guide catheter 1000 may include a pullwire 1120slidably disposed in lumens within the wall of the catheter 1000extending to the distal end 1016. By applying tension to the pullwire1120 in the proximal direction, the distal end 1016 curves in thedirection of the pullwire 1120 as illustrated by arrow 1122. Likewise,as shown in FIG. 46B, placement of the pullwire 1120 along the oppositeside of the catheter 1000 will allow the distal end 1016 to curve in theopposite direction, as illustrated by arrow 1124, when tension isapplied to the pullwire 1120. Thus, referring to FIG. 46C, diametricallyopposing placement of pullwires 1120 within the walls of the catheter1000 allows the distal end 1016 to be steered in opposite directions.This provides a means of correcting or adjusting a curvature. Forexample, if tension is applied to one pullwire to create a curvature,the curvature may be lessened by applying tension to the diametricallyopposite pullwire. Referring now to FIG. 46D, an additional set ofopposing pullwires 1120′ may extend within the wall of the catheter 1000as shown. This combination of pullwires 1120, 1120′ allows curvature ofthe distal end in at least four directions illustrated by arrows 1122,1124, 1126, 1128. In this example, pullwires 1120 create the primarycurve 1100 of the outer guide catheter 1000 and the pullwires 1120′create the lift. It may be appreciated that FIGS. 46A-51D also pertainto the inner guide catheter 1020. For example, in FIG. 46D, pullwires1120 may create the secondary curve 1104 of the inner guide catheter1020 and the pullwires 1120′ create the angle theta 1070.

Such pullwires 1120 and/or pullwires 1120′ and associated lumens may beplaced in any arrangement, singly or in pairs, symmetrically ornonsymmetrically and any number of pullwires may be present. This mayallow curvature in any direction and about various axes. The pullwires1120, 1120′ may be fixed at any location along the length of thecatheter by any suitable method, such as gluing, tying, soldering, orpotting, to name a few. When tension is applied to the pullwire, thecurvature forms from the point of attachment of the pullwire toward theproximal direction. Therefore, curvatures may be formed throughout thelength of the catheter depending upon the locations of the points ofattachment of the pullwires. Typically, however, the pullwires will beattached near the distal end of the catheter, optionally to an embeddedtip ring 280, illustrated in FIG. 46E. As shown, the pullwire 1120passes through an orifice 286 in the tip ring 280, forms a loop shapeand then passes back through the orifice 286 and travels back up throughthe catheter wall (not shown). In addition, the lumens which house thepullwires may be straight, as shown in FIGS. 46A-46D, or may be curved.

D. Catheter Construction

The outer guide catheter 1000 and inner guide catheter 1020 may have thesame or different construction which may include any suitable materialor combination of materials to create the above described curvatures.For clarity, the examples provided will be in reference to the outerguide catheter 1000, however it may be appreciated that such examplesmay also apply to the inner guide catheter 1020.

In embodiments in which the catheter is precurved rather than steerableor in addition to being steerable, the catheter 1000 may be comprised ofa polymer or copolymer which is able to be set in a desired curvature,such as by heat setting. Likewise, the catheter 1000 may be comprised ofa shape-memory alloy.

In embodiments in which the catheter is steerable, the catheter 1000 maybe comprised of one or more of a variety of materials, either along thelength of the catheter 1000 or in various segments. Example materialsinclude polyurethane, Pebax, nylon, polyester, polyethylene, polyimide,polyethylene terephthalate (PET), polyetheretherketone (PEEK). Inaddition, the walls of the catheter 1000 may be reinforced with avariety of structures, such as metal braids or coils. Suchreinforcements may be along the length of the catheter 1000 or invarious segments.

For example, referring to FIG. 47A, the catheter 1000 may have aproximal braided segment 1150, a coiled segment 1152 and distal braidedsegment 1154. The proximal braided segment 1150 provides increasedcolumn strength and torque transmission. The coiled segment 1152provides increased steerability. The distal braided segment 1154provides a blend of steerability and torque/column strength. In anotherexample, referring to FIG. 47B, the outer guiding catheter 1000 has aproximal double-layer braided segment 1151 and a distal braided segment1154. Thus, the proximal double-layer segment 1151 comprises amulti-lumen tube 1160 (having steering lumens 1162 for pullwires, distalends of the steering lumens 1162 optionally embedded with stainlesssteel coils for reinforcement, and a central lumen 1163), an innerbraided layer 1164, and an outer braided layer 1166, as illustrated inthe cross-sectional view of FIG. 47C. Similarly, FIG. 47D provides across-sectional view of the distal braided segment 1154 comprising themulti-lumen tube 1160 and a single braided layer 1168. In a furtherexample, referring to FIG. 47E, the inner guiding catheter 1020comprises a multi-lumen tube 1160 without reinforcement at its proximalend, a single braided layer middle segment 1170 and a single braidedlayer distal segment 1171. Each of the single braided layer segments1170, 1171 have a multi-lumen tube 1160 and a single layer of braiding1168, as illustrated in cross-sectional view FIG. 47F. However, thesegments 1170, 1171 are comprised of polymers of differing durometers,typically decreasing toward the distal end.

FIG. 47G illustrates an other example of a cross-section of a distalsection of an outer guiding catheter 1000. Here, layer 1130 comprises55D Pebax and has a thickness of approximately 0.0125 in. Layer 1131comprises a 30 ppi braid and has a thickness of approximately 0.002 in.by 0.0065 in. Layer 1132 comprises 55D Pebax and has a thickness ofapproximately 0.006 in. Layer 1133 comprises 30 ppi braid and has athickness of approximately 0.002 in by 0.0065 in. And finally, layer1134 comprises Nylon 11 and includes steering lumens for approximately0.0105 in. diameter pullwires 1120. Central lumen 1163 is of sufficientsize for passage of devices.

FIGS. 47H-47I illustrate additional examples of cross-sections of aninner guiding catheter 1020, FIG. 47I illustrating a cross-section of aportion of the distal end and FIG. 47I illustrating a cross-section of amore distal portion of the distal end. Referring to FIG. 47H, layer 1135comprises 40D polymer and has a thickness of approximately 0.0125 in.Layer 1136 comprises a 30 ppi braid and has a thickness of approximately0.002 in. by 0.0065 in. Layer 1137 comprises 40D polymer and has athickness of approximately 0.006 in. Layer 1138 comprises a 40D polymerlayer and has a thickness of approximately 0.0035 in. And finally, layer1139 comprises a 55D liner. In addition, coiled steering lumens areincluded for approximately 0.0105 in. diameter pullwires 1120. And,central lumen 1163 is of sufficient size for passage of devices.Referring to FIG. 47I, layer 1140 comprises a 40D polymer, layer 1141comprises a 35D polymer, layer 1142 comprises a braid and layer 1143comprises a liner. In addition, coiled steering lumens 1144 are includedfor pullwires. And, central lumen 1163 is of sufficient size for passageof devices.

FIGS. 48A-48C illustrate an embodiment of a keying feature which may beincorporated into the catheter shafts. The keying feature is used tomaintain relationship between the inner and outer guide catheters toassist in steering capabilities. As shown in FIG. 48A, the inner guidecatheter 1020 includes one or more protrusions 1400 which extendradially outwardly. In this example, four protrusions 1400 are present,equally spaced around the exterior of the catheter 1020. Likewise, theouter guide catheter 1000 includes corresponding notches 1402 whichalign with the protrusions 1400. Thus, in this example, the catheter1000 includes four notches equally spaced around its central lumen 1018.Thus, the inner guide catheter 1020 is able to be translated within theouter guide catheter 1000, however rotation of the inner guide catheter1020 within the outer guide catheter 1000 is prevented by the keyingfeature, i.e. the interlocking protrusions 1400 and notches 1402. Suchkeying helps maintain a known correlation of position between the innerguide catheter 1020 and outer guide catheter 1000. Since the inner andouter guide catheters 1020, 1000 form curvatures in differentdirections, such keying is beneficial to ensure that the compoundcurvature formed by the separate curvatures in the inner and outer guidecatheters 1020, 1000 is the compound curvature that is anticipated.Keying may also increase stability wherein the curvatures remain inposition reducing the possibility of compensating for each other.

FIG. 48B illustrates a cross-sectional view of the outer guidingcatheter 1000 of FIG. 48A. Here, the catheter 1000 includes a notchedlayer 1404 along the inner surface of central lumen 1018. The notchedlayer 1404 includes notches 1402 in any size, shape, arrangement andnumber. Optionally, the notched layer 1404 may include lumens 1406,typically for passage of pullwires 1120. However, the lumens 1406 mayalternatively or in addition be used for other uses. It may also beappreciated that the notched layer 1404 may be incorporated into thewall of the catheter 1000, such as by extrusion, or may be a separatelayer positioned within the catheter 1000. Further, it may beappreciated that the notched layer 1404 may extend the entire length ofthe catheter 1000 or one or more portions of the length of the catheter1000, including simply a small strip at a designated location along thelength of the catheter 1000.

FIG. 48C illustrates a cross-sectional view of the inner guidingcatheter 1020 of FIG. 48A. Here, the catheter 1020 includes protrusions1400 along the outer surface of the catheter 1020. The protrusions 1400may be of any size, shape, arrangement and number. It may be appreciatedthat the protrusions 1400 may be incorporated into the wall of thecatheter 1020, such as by extrusion, may be included in a separatecylindrical layer on the outer surface of the catheter 1020, or theprotrusions 1400 may be individually adhered to the outer surface of thecatheter 1020. Further, it may be appreciated that the protrusions 1400may extend the entire length of the catheter 1000 or one or moreportions of the length of the catheter 1020, including simply a smallstrip at a designated location along the length of the catheter 1020.

Thus, the keying feature may be present along one or more specificportions of the catheters 1000, 1020 or may extend along the entirelength of the catheters 1000, 1020. Likewise, the notches 1402 mayextend along the entire length of the outer guiding catheter 1020 whilethe protrusions 1400 extend along discrete portions of the inner guidingcatheter 1000 and vice versa. It may further be appreciated that theprotrusions 1400 may be present on the inner surface of the outerguiding catheter 1000 while the notches 1402 are present along the outersurface of the inner guiding catheter 1020.

Alternatively or in addition, one or more steerable portions of thecatheter 1000 may comprise a series of articulating members 1180 asillustrated in FIG. 49A. Exemplary embodiments of steerable portions ofcatheters comprising such articulating members 1180 are described inU.S. Pat. No. 7,682,319 (Attorney Docket No. 020489-001210US)incorporated herein by reference for all purposes. FIG. 49B illustratesthe outer guide catheter 1000 having a steerable portion comprisingarticulating members 1180 at its distal end 1016.

Briefly, referring to FIG. 49A, each articulating member 1180 may haveany shape, particularly a shape which allows interfitting or nesting asshown. In addition, it is desired that each member 1180 have thecapability of independently rotating against an adjacent articulatingmember 1180. In this embodiment, the articulating members 1180 compriseinterfitting domed rings 1184. The domed rings 1184 each include a base1188 and a dome 1186. The base 1188 and dome 1186 have a hollow interiorwhich, when the domed rings 1184 are interfit in a series, forms acentral lumen 1190. In addition, the dome 1186 allows each articulatingmember 1180 to mate against an inner surface of an adjacent domed ring1184.

The interfitting domed rings 1184 are connected by at least one pullwire1120. Such pullwires typically extend through the length of the catheter1000 and at least one of the interfitting domed rings 1184 to a fixationpoint where the pullwire 1120 is fixedly attached. By applying tensionto the pullwire 1120, the pullwire 1120 arcs the series of interfittingdomed rings 1184 proximal to the attachment point to form a curve. Thus,pulling or applying tension on at least one pullwire, steers or deflectsthe catheter 1000 in the direction of that pullwire 1120. By positioningvarious pullwires 1120 throughout the circumference of the domed rings1184, the catheter 1000 may be directed in any number of directions.

Also shown in FIG. 49A, each interfitting domed ring 1184 may compriseone or more pullwire lumens 1182 through which the pullwires 1120 arethreaded. Alternatively, the pullwires 1120 may be threaded through thecentral lumen 1190. In any case, the pullwires are attached to thecatheter 1000 at a position where a desired curve is to be formed. Thepullwires 1120 may be fixed in place by any suitable method, such assoldering, gluing, tying, welding or potting, to name a few. Suchfixation method is typically dependent upon the materials used. Thearticulating members 1180 may be comprised of any suitable materialincluding stainless steel, various metals, various polymers orco-polymers. Likewise the pullwires 1120 may be comprised of anysuitable material such as fibers, sutures, metal wires, metal braids, orpolymer braids.

E. Handles

As mentioned previously, manipulation of the guide catheters 1000, 1020is achieved with the use of handles 1056, 1057 attached to the proximalends of the catheters 1000, 1020. FIG. 50 illustrates a preferredembodiment of handles 1056, 1057. As shown, handle 1056 is attached tothe proximal end 1014 of outer guide catheter 1000 and handle 1057 isattached to the proximal end 1024 of inner guide catheter 1020. Innerguide catheter 1020 is inserted through handle 1056 and is positionedcoaxially within outer guide catheter 1000. In this embodiment, thehandles 1056, 1057 are not linked together as shown in the embodimentillustrated in FIG. 42. It may be appreciated that such handles 1056,1057 may alternatively be connected by external connecting rods, bars orplates or by an additional external stabilizing base. An embodiment of astabilizing base will be described in a later section. Referring back toFIG. 50, interventional catheter is inserted through handle 1057 and ispositioned coaxially within inner guide catheter 1020 and outer guidecatheter 1000.

Each handle 1056, 1057 includes two steering knobs 1300 a, 1300 bemerging from a handle housing 1302 for manipulation by a user. Steeringknobs 1300 a are disposed on a side of the housing 1302 and steeringknobs 1300 b are disposed on a face of the housing 1302. However, it maybe appreciated that such placement may vary based on a variety offactors including type of steering mechanism, size and shape of handle,type and arrangement of parts within handle, and ergonomics to name afew.

FIG. 51 illustrates the handles 1056, 1057 of FIG. 50 with a portion ofthe housing 1302 removed to reveal the assemblies of the handles. Eachknob 1300 a, 1300 b controls a steering mechanism which is used to forma curvature in the attached catheter. Each steering mechanism includes ahard stop gear assembly 1304 and a friction assembly 1306. Tension isapplied to one or more pullwires by action of the hard stop gearassembly to form a curve in a catheter. Tension is maintained by thefriction assembly. When tension is released from the one or morepullwires the catheter returns to a straightened position.

FIG. 52 illustrates steering mechanisms within a handle wherein thehousing 1302 is removed for clarity. Here, steering knob 1300 a isattached to a hard stop gear assembly 1304 and a friction assembly (notin view) and steering knob 1300 b is attached to a separate hard stopgear assembly 1304 and friction assembly 1306. Steering knob 1300 a isattached to a knob post 1318 which passes through a base 1308,terminating in a knob gear wheel 1310. The knob gear wheel 1310 actuatesthe hard stop gear assembly 1304, thereby applying tension to one ormore pullwires 1120.

The knob gear wheel 1310 is a toothed wheel that engages a disk gearwheel 1312. Rotation of the steering knob 1300 a rotates the knob post1318 and knob gear wheel 1310 which in turn rotates the disk gear wheel1312. Rotation of the disk gear wheel 1312 applies tension to one ormore pullwires extending through the attached catheter, in this examplethe outer guiding catheter 1000. As shown, the outer guiding catheter1000 passes through the base 1308, wherein one or more pullwires 1120extending through the catheter 1000 are attached to the disk 1314. Suchattachment is schematically illustrated in FIG. 53. Catheter 1000 isshown passing through base 1308. A pullwire 1120 passing through asteering lumen 1162 in the catheter 1000 emerges from the wall of thecatheter 1000, passes through an aperture 1320 in the disk 1314 and isattached to an anchor peg 1316 on the disk 1314. Rotation of the disk1314 (indicated by arrow 1328) around disk post 1315 by action of thedisk gear wheel 1312, applies tension to the pullwire 1120 by drawingthe pullwire 1120 through the aperture 1320 and wrapping the pullwire1120 around the disk 1314 as it rotates. Additional rotation of the disk1314 applies increasing tension to the pullwire 1120. To limit theamount of tension applied to the pullwire 1120, to limit curvature ofthe catheter and/or to avoid possible breakage of the pullwire 1120, therotation of the disk 1314 may be restricted by hard stop peg 1322 whichis attached to the disk 1314 and extends into the base 1308.

FIGS. 54A-54B illustrate how the hard stop peg 1322 is used to restrictrotation of disk 1314. FIGS. 54A-54B provide a top view, wherein thedisk 1314 is disposed on the base 1308. The anchor peg 1316 is shownwith the pullwire 1120 thereattached. A groove 1326 is formed in thebase 1308 beneath the disk 1314 and forms an arc shape. The hard stoppeg 1322 extends from the disk 1314 into the groove 1326 in the base1308. Referring now to FIG. 54B, rotation of the disk 1314 around knobpost 1318, indicated by arrow 1330, draws the pullwire 1120 through theaperture 1320 as previously described, wrapping the pullwire 1120 aroundthe disk 1314. As the disk 1314 rotates, the hard stop peg 1322 followsalong the groove 1326, as shown. The disk 1314 continues rotating untilthe hard stop peg 1322 reaches a hard stop 1324. The hard stop 1324 ispositioned in the groove 1326 and prevents further passage of the hardstop peg 1322. Thus, disk 1314 rotation may be restricted to any degreeof rotation less than or equal to 360 degrees by positioning of the hardstop 1324.

In some instances, it is desired to restrict rotation of the disk 1314to a degree of rotation which is more than 360 degrees. This may beachieved with another embodiment of the hard stop gear assembly 1304.Referring now to FIGS. 55A-55B, a portion of such a hard stop gearassembly 1304 is shown. FIG. 55A illustrates the base 1308 and the diskpost 1315 positioned therethrough. Also shown in the base 1308 is anaperture 1334 through which the knob post 1318, knob gear wheel 1310 andfriction assembly 1306 pass, and a passageway 1336 through which thecatheter 1000 passes. In this embodiment of the hard stop gear assembly1304, a groove 1326 is also present in an arc shape around the disk post1315, however a ball 1332 is positioned in the groove 1326 rather than ahard stop peg 1322. Disk 1314 is positioned over the groove 1326 and theball 1332 as shown in FIG. 55B. The disk 1314, illustrated in FIG. 55C,has a groove 1356 in its surface which is positioned adjacent to thebase 1308, the groove 1356 having an arc shape similar to the groove1326 in the base 1308. The ball 1332 is not fixedly attached to the base1308 or the disk 1314 and is therefore free to move along the channelformed by the groove 1326 in the base 1308 and the groove in the disk1314.

FIGS. 56A-56F illustrate how rotation of the disk 1314 may be restrictedby the ball 1332 to a degree of rotation which is more than 360 degrees.FIGS. 56A-56F illustrate the groove 1326 in the base 1308 wherein thegroove 1326 has an arc shape around disk post 1315. The groove 1326 doesnot form a complete circle; a first groove end 1350 a and a secondgroove end 1350 b form a wall which prevent passage of the ball 1332. Itmay be appreciated that the groove ends 1350 a, 1350 b may be anydistance apart, shortening the length of the groove 1326 by any amount,and allowing the ball 1332 movement, and hence catheter deflection, tobe adjusted to any desired amount. To begin, referring to FIG. 56A, theball 1332 is positioned within the groove 1326 near the first groove end1350 a. The disk 1314 has a matching groove 1352 (shape illustrated indashed line) including a first groove end 1354 a and a second groove end1354 b. The disk 1314 is positioned over the ball 1332 so that the ball1332 is near the second groove end 1354 b.

Referring now to FIG. 56B, the disk 1314 may be rotated while the ball1332 remains in place. Here, the disk 1314 has rotated 90 degrees, asindicated by arrow 36000 and the position of the groove ends 1354 a,1354 b. Referring now to FIG. 56C, the disk 1314 may be further rotatedwhile the ball 1332 remains in place. Here, the disk 1314 has rotated270 degrees, as indicated by arrow 36000 and the position of the grooveends 1354 a, 1354 b. The disk 1314 may continue rotating to 360 degrees,as shown in FIG. 56D, indicated by arrow 36000. Here, the first grooveend 1354 a in the disk 1314 has contacted the ball 1332 and pushes theball 1332 along groove 1326 in the base. Referring now to FIG. 56E, thedisk 1314 may be further rotated while the ball 1332 is pushed along thegroove 1326 in the base 1308 by the first groove end 1354 a in the disk1314. Here, the disk 1314 is shown to have rotated 540 degrees.Referring to FIG. 56F, the disk 1314 rotates until the ball 1332 reachesthe second groove end 1350 b of the base 1308, providing a hard stop. Inthis position, the ball 1332 is held between the first groove end 1354 aof the disk 1314 and the second groove end 1350 b of the base 1308 andfurther rotation of the disk 1314 is prevented. Thus, the disk 1314 wasrotated approximately 660 degrees in this example. Any maximum degree ofrotation may be set by positioning of groove ends 1350 a, 1350 b and/orgroove ends 1354 a, 1354 b. Additionally, in some embodiments, rotationcan be limited by adding more than one ball 1332 to the groove 1326, forexample, two, three, four, five, six, seven, eight, nine, ten or moreballs may be used to limit travel and hence curvature.

It may be appreciated that one or more pullwires 1120 are attached tothe disk 1314 in a manner similar to that illustrated in FIG. 53.Therefore, as the disk 1314 rotates, around disk post 1315 by action ofthe disk gear wheel 1312, tension is applied to the pullwire 1120 bydrawing the pullwire 1120 through the aperture 1320 and wrapping thepullwire 1120 around the disk 1314 as it rotates. Additional rotation ofthe disk 1314 applies increasing tension to the pullwire 1120.Restriction of rotation as described above limits the amount of tensionapplied to the pullwire 1120, to limit curvature of the catheter and/orto avoid possible breakage of the pullwire 1120.

As mentioned, each steering mechanism includes at least a hard stop gearassembly 1304 and a friction assembly 1306. As described above, tensionis applied to one or more pullwires by action of the hard stop gearassembly to form a curve in a catheter. Tension is maintained by thefriction assembly. FIG. 57 illustrates an embodiment of a frictionassembly 1306. The friction assembly 1306 essentially holds a steeringknob, in this example steering knob 1300 b, and the associated knob post1318 in a rotated position. Here, rotation of the knob 1300 b and post1318 rotates attached knob gear wheel 1310. The knob gear wheel 1310actuates the hard stop gear assembly 1304, thereby applying tension toone or more pullwires 1120. The knob gear wheel 1310 is a toothed wheelthat engages a disk gear wheel 1312. Rotation of the steering knob 1300b rotates the knob post 1318 and knob gear wheel 1310 which in turnrotates the disk gear wheel 1312. Rotation of the disk gear wheel 1312applies tension to one or more pullwires extending through the attachedcatheter, in this example the outer guiding catheter 1000.

The steering knob 1300 b and knob post 1318 are held in a rotatedposition by friction provided by a frictional pad 1370. The frictionalpad 1370 is positioned between ring 1372 attached to the knob post 1318and a plate 1374 attached to the base 1308. The knob post 1318 extendsfrom the knob 1300 b through the ring 1372, the frictional pad 1370 andthen the plate 1374. The plate 1374 has internal threads which mate withthreads on the knob post 1318. As the knob post 1318 rotates, thethreads on the post 1318 advance through the threads on the plate 1374.This draws the ring 1372 closer to the plate 1374, compressing thefrictional pad 1370 therebetween. Frictional pad 1370 may be comprisedof any O-ring or sheet material with desirable frictional andcompressibility characteristics, such as silicone rubber, natural rubberor synthetic rubbers, to name a few. In preferred embodiments, an EPDMrubber O-ring is used. Reverse rotation of the knob post 1318 isresisted by friction of the frictional pad 1370 against the ring 1372.The higher the compression of the frictional pad 1370 the stronger thefrictional hold. Therefore, as the steering knob 1300 b is rotated andincreasing amounts of tension are applied to the pullwires 1120,increasing amounts of friction are applied to the ring 1372 to hold theknob 1300 b in place.

Manual reverse rotation of the steering knob 1300 b releases tension onthe pullwires 1120 and draws the ring 1372 away from the plate 1374thereby reducing the frictional load. When tension is released from thepullwires 1120 the catheter 1000 returns toward a straightened position.

It may be appreciated that each handle 1056, 1057 includes a steeringmechanism for each curve to be formed in the attached catheter. Thus, asshown in FIG. 51, handle 1056 includes a steering mechanism to form theprimary curve 1100 in outer guiding catheter 1000 and a steeringmechanism to form the additional curve 1110. Likewise, handle 1057includes a steering mechanism to form the secondary curve 1104 in innerguiding catheter 1020 and a steering mechanism to form the angle theta1070.

Some curves, such as the primary curve 1100, secondary curve 1104 andadditional curve 1110 each typically vary in curvature between astraight configuration and a curved configuration in a single direction.Such movement may be achieved with single set of a hard stop gearassembly 1304 and a friction assembly 1306. However, other curves, suchas the angle theta 1070, may be formed in two directions as shown inFIGS. 43C-43D. Such movement is achieved with two sets of the hard stopgear assembly 1304 and the friction assembly 1306, each set controllingcurvature in a single direction.

FIG. 57 illustrates the presence of an additional set of the frictionassembly 1306′. One or more pullwires 1120′, such as an opposing set asillustrated in FIG. 46D, extending within the wall of the catheter 1000are attached to the disk 1314′ in the same manner as pullwires 1120 areattached to disk 1314. The disks 1314, 1314′ are arranged so thatrotation of steering knob 1300 b in one direction applies tension to thepullwires 1120 via disk 1314 and rotation of steering knob 1300 b in theopposite direction applies tension to the pullwires 1120′ via disk1314′. Likewise, the additional friction assembly 1306′ is shown havinga ring 1372′ attached to the knob post 1318 and a frictional pad 1370′disposed between the ring 1372′ and the opposite side of the plate 1374.Therefore, as rotation of the steering knob 1300 b in the oppositedirection applies tension to the pullwires 1120′ via disk 1314′, thefrictional pad 1370′ applies tension to the ring 1372′ holding the knobpost 1318′ in place.

It may be appreciated that various other mechanisms may be used fortensioning and holding pullwires 1120 in place. Example mechanisms thatmay alternatively be used include clutches, ratchets, levers, knobs,rack and pinions, and deformable handles, to name a few.

F. Interventional System

FIG. 58 illustrates an embodiment of an interventional system 3 of thepresent invention. An embodiment of the multi-catheter guiding system 1of the present invention is shown comprising an outer guide catheter1000, having a proximal end 1014 and a distal end 1016, and an innerguide catheter 1020, having a proximal end 1024 and a distal end 1026,wherein the inner guide catheter 1020 is positioned coaxially within theouter guide catheter 1000, as shown. In addition, a hemostatic valve1090 is disposed within handle 1056 or external to handle 1056 as shownto provide leak-free sealing with or without the inner guide catheter1020 in place. The valve 1090 also prevents back bleeding and reducesthe possibility of air introduction when inserting the inner guidecatheter 1020 through the outer guide catheter 1000. An example of ahemostatic valve 1090 is illustrated in FIG. 58A, however any suitablevalve or hemostatic valve may be used to provide similar functions. InFIG. 58A, the valve 1090 has a first end 1091, a second end 1092 and alumen 1093 therethrough. The inner wall of lumen 1093 is preferablytapered toward end 1091 and may further include a plurality of taperedaxial channels configured to receive the protrusions 1400 on the innerguide catheter 1020. The first end 1091 is attached to the outer guidecatheter 1000 and the second end 1092 is free. Referring now back toFIG. 58, the distal ends 1016, 1026 of catheters 1000, 1020,respectively, are sized to be passable to a body cavity, typicallythrough a body lumen such as a vascular lumen.

To assist in inserting the fixation device 14 through a hemostatic valve1090, a fixation device introducer may be used. For example, when thefixation device 14 is loaded on a delivery catheter 300 and an innerguide catheter 1020, insertion of the fixation device 14, deliverycatheter 300 and inner guide catheter 1020 through an outer guidecatheter 1000 involves passing the fixation device 14 through ahemostatic valve 1090 on the outer guide catheter 1000. To reduce anytrauma to the fixation device 14 by the hemostatic valve 1090, afixation device introducer may be used. An embodiment of a fixationdevice introducer 1420 is illustrated in FIG. 58B. The introducer 1420includes a loading body 1422 and an insertion endpiece 1424. Thefixation device 14 is loaded into the loading body 1422 and into theinsertion endpiece 1424 to approximately the dashed line 1428. Theinsertion endpiece 1424 has a split end creating individual splitsections 1430, in this embodiment, four split sections 1430. Bycompressing the split sections 1430, the endpiece 1424 forms a taper.Such a taper is then inserted through a hemostatic valve 1090, so thatthe insertion endpiece 1424 creates a smooth passageway through thevalve for the fixation device 14. Once the insertion endpiece 1424 isinserted through the valve 1090, the fixation device 14, and attacheddelivery catheter 300 and inner guide catheter 1020, may then beadvanced through the fixation device introducer 1420. The fixationdevice introducer 1420 also includes a hemostatic valve within theloading body 1422 to prevent any backbleeding or leakage through theintroducer 1420.

Manipulation of the guide catheters 1000, 1020 is achieved with the useof handles 1056, 1057 attached to the proximal ends of the catheters1000, 1020. As shown, handle 1056 is attached to the proximal end 1014of outer guide catheter 1000 and handle 1057 is attached to the proximalend 1024 of inner guide catheter 1020. Inner guide catheter 1020 isinserted through handle 1056 and is positioned coaxially within outerguide catheter 1000.

An embodiment of the delivery catheter 300 of the present invention isinserted through handle 1057 and is positioned coaxially within innerguide catheter 1020 and outer guide catheter 1000. Therefore, ahemostatic valve 1090 is disposed within handle 1057 or external tohandle 1057 as shown to provide leak-free sealing with or without thedelivery catheter 300 in place. The valve 1090 functions as describedabove. The delivery catheter 300 includes a shaft 302, having a proximalend 322 and a distal end 324, and a handle 304 attached to the proximalend 322. A fixation device 14 is removably coupled to the distal end 324for delivery to a site within the body.

The outer guide catheter 1000 and/or the inner guide catheter 1020 areprecurved and/or have steering mechanisms to position the distal ends1016, 1026 in desired directions. Precurvature or steering of the outerguide catheter 1000 directs the distal end 1016 in a first direction tocreate a primary curve while precurvature and/or steering of the innerguide catheter 1020 directs distal end 1026 in a second direction,differing from the first, to create a secondary curve. Together, theprimary and secondary curves form a compound curve. Advancement of thedelivery catheter 300 through the coaxial guide catheters 1000, 1020guides the delivery catheter 300 through the compound curve toward adesired direction, usually in a direction which will position thefixation device 14 in a desired location within the body.

FIG. 59 illustrates portions of another embodiment of an interventionalsystem 3 of the present invention. Handles 1056, 1057 of themulti-catheter guiding system 1 of the present invention are shown. Eachhandle 1056, 1057 includes a set of steering knobs 1300 a, 1300 b, asshown. Manipulation of the guide catheters 1000, 1020 is achieved withthe use of the steering knobs 1300 a, 1300 b attached to the proximalends of the catheters 1000, 1020. Handle 304 of the delivery catheter300 is also shown, including the proximal element line handle 312, thelock line handle 310, the actuator rod control 314 and the actuator rodhandle 316, among other features. The handle 304 is supported by thesupport base 306 which is connected to the handle 1057.

It may be appreciated the above described systems 3 are not intended tolimit the scope of the present invention. The systems 3 may include anyor all of the components of the described invention. In addition, themulti-catheter guiding system 1 of the present invention may be used tointroduce other delivery catheters, interventional catheters or otherdevices. Likewise, the delivery catheter 300 may be introduced throughother introducers or guiding systems. Also, the delivery catheter 300may be used to deliver other types of devices to a target locationwithin the body, including endoscopic staplers, devices forelectrophysiology mapping or ablation, septal defect repair devices,heart valves, annuloplasty rings and others.

In addition, many of the components of the system 3 may include one ormore hydrophilic coatings. Hydrophilic coatings become slippery whenwet, eliminate the need for separate lubricants. Thus, such coatings maybe present on the multi-catheter guiding system, delivery catheter, andfixation device, including the proximal elements and distal elements, toname a few.

Further, the system 3 may be supported by an external stabilizer base1440, an embodiment of which is illustrated in FIG. 60. Stabilizer base1440 maintains the relative positions of the outer guide, inner guideand delivery catheter during a procedure. In this embodiment, the base1440 comprises a platform 1442 having a planar shape for positioning onor against a flat surface, such as a table or benchtop. The base 1440further includes a pair of handle holders 1444, 1448, each attached tothe platform 1442 and extending upwardly from the platform 1442, eitherangularly or perpendicularly. Handle holder 1444 includes a notch 1446for holding the outer guiding catheter 1000, as illustrated in FIG. 61,thereby supporting the handle 1056. FIG. 61 shows the handle 1056attached to the outer guiding catheter 1000 positioned so that theproximal end 1014 of the outer guiding catheter 1000 rests in the notch1446. Referring back to FIG. 60, handle holder 1448 includes an elongateportion 1452 having a trough 1450 and a hooked end 1454. As shown inFIG. 62, handle 1057 rests on the elongate portion 1452 and the handle304 rests on hooked end 1454 so that the inner guiding catheter 1020extends from the handle 1057 to the handle 1056 and continues on withinouter guiding catheter 1000. The handle 304 is additionally supported bysupport base 306, as shown.

It may be appreciated that the stabilizer base 1440 may take a varietyof forms and may include differences in structural design to accommodatevarious types, shapes, arrangements and numbers of handles.

G. Kits

Referring now to FIG. 63, kits 1500 according to the present inventioncomprise any of the components described in relation to the presentinvention. The kits 1500 may include any of the components describedabove, such as the outer guide catheter 1000 including handle 1056, theinner guide catheter 1020 including handle 1057, the delivery catheter300 and the fixation device 14 and instructions for use IFU. Optionally,any of the kits may further include any other system componentsdescribed above, such as various interventional tools 1040, orcomponents associated with positioning a device in a body lumen, such asa guidewire 1202, dilator 1206 or needle 1204. The instructions for useIFU will set forth any of the methods as described above, and all kitcomponents will usually be packaged together in a pouch 1505 or otherconventional medical device packaging. Usually, those kit componentswhich will be used in performing the procedure on the patient will besterilized and maintained within the kit. Optionally, separate pouches,bags, trays or other packaging may be provided within a larger package,where the smaller packs may be opened separately to separately maintainthe components in a sterile fashion.

While the foregoing is a complete description of the preferredembodiments of the invention, various alternatives, substitutions,additions, modifications, and equivalents are possible without departingfrom the scope of the invention. For example, in many of theabove-described embodiments, the invention is described in the contextof approaching a valve structure from the upstream side—that is, theatrial side in the case of a mitral valve. It should be understood thatany of the foregoing embodiments may be utilized in other approaches aswell, including from the ventricular or downstream side of the valve, aswell as using surgical approaches through a wall of the heart. Moreover,the invention may be used in the treatment of a variety of other tissuestructures besides heart valves, and will find usefulness in a varietyof tissue approximation, attachment, closure, clamping and ligationapplications, some endovascular, some endoscopic, and some opensurgical.

Again, although the foregoing invention has been described in somedetail by way of illustration and example, for purposes of clarity ofunderstanding, it will be obvious that various alternatives,modifications and equivalents may be used and the above descriptionshould not be taken as limiting in scope of the invention which isdefined by the appended claims.

What is claimed is:
 1. A system for approximating tissue, said systemcomprising: a delivery catheter having a lumen extending therethrough;an actuator rod disposed at least partially in the lumen, and having aproximal end and a distal end; a flexible cable at least partiallydisposed in the lumen, the flexible cable having a proximal end and adistal end, wherein the proximal end of the flexible cable is coupled tothe distal end of the actuator rod, and wherein the flexible cable isresiliently biased to return to a substantially linear configurationafter being deflected 90° or more; a coupler coupled to the distal endof the flexible cable; and an implantable fixation device releasablyattached to the coupler.
 2. The system of claim 1, wherein when rotated,the actuator rod transmits a torque ranging from at least 0.25inch-ounces to 0.74 inch-ounces with a substantially 1 to 1 torquetransmission ratio from the proximal end of the actuator rod to thedistal end of the actuator rod.
 3. The system of claim 1, wherein theactuator rod transmits at least 1 pound of compressive force to theimplantable fixation device without substantial buckling of the rod. 4.The system of claim 1, wherein the actuator rod can withstand at least 5pounds of tensile force without substantial elongation of the rod. 5.The system of claim 1, wherein the flexible cable comprises a strandedcable.
 6. The system of claim 1, wherein the flexible cable comprises aplurality of wires wound in a helix.
 7. The system of claim 1, whereinthe flexible cable comprises an inner core cable, the inner core cablecomprising a plurality of wires.
 8. The system of claim 1, wherein atleast half of a torque applied to the proximal end of the flexible cableis transmitted to the distal end thereof when the flexible cable istorqued in a first direction.
 9. The system of claim 8, whereinsubstantially all of the torque is transmitted from the proximal end tothe distal end of the flexible cable.
 10. The system of claim 1, whereinthe flexible cable comprises a plurality of wires wound in a firstdirection, and wherein the flexible cable transmits torque in the firstdirection with a higher torque transmission ratio than in a seconddirection opposite the first direction.
 11. The system of claim 1,wherein the coupler comprises a proximal bore and a distal bore, andwherein the distal end of the cable is disposed in the proximal bore,and a portion of the fixation device is disposed in the distal bore. 12.The system of claim 1, wherein the coupler comprises an enlargedproximal cylindrical portion and a smaller distal cylindrical portion.13. The system of claim 12, wherein the enlarged proximal portion issubstantially the same diameter as the smaller distal cylindricalportion after the proximal portion has been swaged to the flexiblecable.
 14. The system of claim 1, wherein the coupler has a first endand a second end opposite thereof, and wherein the first end of thecoupler is swaged to the flexible cable, and the second end of thecoupler is releasably attached to the fixation device.
 15. The system ofclaim 1, wherein the coupler has a first end and a second end oppositethereof, and wherein the first end is fixedly attached to the flexiblecable, and the second end of the coupler is releasably attached to thefixation device.
 16. The system of claim 15, wherein the second end ofthe coupler is threadably coupled to the fixation device.
 17. The systemof claim 1, wherein the implantable fixation device comprises: a pair offixation elements each having a first end, a free end opposite the firstend, and an engagement surface therebetween for engaging the tissue, thefirst ends being movably coupled together such that the fixationelements are moveable between a closed position wherein the engagementsurfaces face each other to an inverted position wherein the engagementsurfaces face away from each other; and an actuation mechanism coupledto the fixation elements adapted to move the fixation elements betweenthe closed position and the inverted position.
 18. The system of claim17, wherein the implantable fixation device further comprises a pair ofgripping elements, each gripping element moveable with respect to one ofthe fixation elements and being disposed in opposition to one of theengagement surfaces so as to capture tissue therebetween.
 19. The systemof claim 18, wherein each fixation element is at least partially concaveand each gripping element is at least partially recessed within thefixation element in a deployed configuration.
 20. The system of claim 1,further comprising a sleeve, the sleeve joining the proximal end of theflexible cable with the distal end of the actuator rod.
 21. The systemof claim 20, wherein the sleeve is fixedly attached to the flexiblecable and the actuator rod.
 22. The system of claim 21, wherein thesleeve comprises a central bore therethrough, and wherein the proximalend of the flexible cable and the distal end of the actuator rod aredisposed in the central bore.
 23. The system of claim 21, wherein thesleeve is swaged to both the flexible cable and the actuator rod.